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molecular characterisation and localisation of an onchocerca volvulus pi-class glutathione s-transferase.glutathione s-transferases (gsts) constitute a major detoxification mechanism in helminth organisms and are regarded vaccine candidates against helminth infections. onchocerca volvulus glutathione-binding proteins were purified from the aqueous soluble fraction of homogenised adult females by affinity chromatography on glutathione-agarose. the eluted proteins had a specific gst activity of 1.6 mumol min-1 mg-1. immunohistochemical studies localised these antigens in the hypodermis, the wall of t ...19947984170
turnover of microfilariae in small mammals. 1. disintegration of microfilariae (litomosoides sigmodontis) (filarioidea: nematoda) after intravenous injection into sigmodon hispidus, the cotton rat.after i.v. injection of 833 x 10(3) microfilariae (mf) per animal (150 g) into naive recipient cotton rats, at autopsy 15 min thereafter 30.4% of them could be recovered as a total: 19.1% were proved in the peripheral circulating blood (pcb) completely intact. 6.5% were recovered by perfusion of the lungs, of which 3/5 were associated with adherent macrophages and neutrophils or partly disintegrated. by perfusion of the liver only 3.8% were obtained, in spite of the four times greater volume of ...19938134771
effect of ivermectin on two filaria-vector pairs. brugia malayi-aedes aegypti; litomosoides sigmodontis-bdellonyssus bacoti.the effect of ivermectin was studied on two filaria-vector pairs, brugia malayi-aedes aegypti and litomosoides sigmodontis-bdellonyssus bacoti. the rodent hosts, respectively mastomys coucha and meriones unguiculatus, were treated with ivermectin doses of 0.05 mg/kg, or 0.2 mg/kg or 2 mg/kg. batches of vectors were fed on rodents, infected or not, treated or not, from h7 to d43 post-ivermectin. vector survival was observed and dissections were performed to study the filarial development. it appe ...19938215116
the putatively protective onchocerca volvulus neuronal protein e1 is a member of the death domain protein family.here we show that e1, an ankyrin-related, potentially protective, neuronal protein of the human filarial nematode onchocerca volvulus contains a death domain (dd), most similar to that of human mort1/fadd (39% identity). in addition, sequence comparison of e1 to its homologue from litomosoides sigmodontis and to caenorhabditis elegans ankyrin defines two further putative functional domains. one represents the end of the spectrin-binding domain of ankyrins, the other an unique domain, most highly ...19968706821
the fate of the filaria litomosoides sigmodontis in susceptible and naturally resistant mice.the fate of litomosoides sigmodontis was compared in susceptible balb/c and resistant b10d2 mice, presenting the same major histocompatibility complex (h-2d), with an attempt to dissociate the different elements of the life cycle in order, later, to dissociate the different mechanisms involved. each female mouse was inoculated once with a small dose of infective larvae (25 l3) or a large dose (100 or 200 l3). in total, 92 balb/c and 49 b10d2 were studied. necropsies were performed up to d85 foll ...19968731760
expression of the microfilarial sheath protein 2 (shp2) of the filarial parasites litomosoides sigmodontis and brugia malayi.the microfilarial sheaths of the filarial parasites brugia malayi, brugia pahangi, and litomosoides sigmodontis consist of several parasite proteins, probably ranging between 7 and 10. the gene encoding sheath protein 2 (shp2), which is the object of this study, is transcribed in embryos and in the uterine epithelium; at least in b. malayi, it is translated in both tissues. apparently, shp2 is synthesized as a monomer, exported by the respective cells, and integrated into the microfilarial sheat ...19979085921
immune responses to filarial infection in laboratory mice.models of filarial infection in laboratory inbred mice are valuable tools for assessing the relevance of anti-filarial immune responses in protection against these parasites. however, laboratory mice are not permissive for those filarial species which are known to infect humans. therefore, immunity to the different stages of these filariae, i.e. infective third stage larvae (l3), adults and microfilariae, has been analyzed separately, as a surrogate approach. although much information has been g ...19979138292
molecular phylogenetic studies on filarial parasites based on 5s ribosomal spacer sequences.this paper is the first large-scale molecular phylogenetic study on filarial parasites (family onchocercidae) which includes 16 species of 6 genera: brugia beaveri ash et little, 1962, b. buckleyi dissanaike et paramananthan, 1961; b. malayi (brug, 1927) buckley, 1960; b. pahangi (buckley et edeson, 1956) buckley, 1960; b. patei (buckley, nelson et heisch, 1958) buckley, 1960; b. timori partono et al, 1977; wuchereria bancrofti (cobbold, 1877) seurat, 1921: w. kalimantani palmieri. purnomo, denn ...19949140481
larval biology of six filariae of the sub-family onchocercinae in a vertebrate host.the development of six filariae of the sub-family onchocercinae-litomosoides sigmodontis, acanthocheilonema viteae, molinema dessetae, monanema martini, brugia malayi, b. pahangi-was compared in rodents, following a single inoculation of a low or high dose of infective larvae. analysis was done with 105 rodents dissected and 53 rodents fixed for histopathology. the percentage of larvae which developed corresponded to the proportion of those which were able to penetrate into the sub-cutaneous lym ...19949140491
immune response to the filaria litomosoides sigmodontis in susceptible and resistant mice.comparisons were made between the immune responses evoked during the course of chronic and patient infections of litomosoides sigmodontis in susceptible balb/c mice and non-patent infections in resistant b10.d2 mice. early antigen specific responses of spleen cells were weak in both mouse strains. however, by day 58 post infection a strong th2 response, as determined by production of il-4, il-5 and il-10, was observed in balb/c mice but not in b10.d2 mice. antibody responses seemed to appear soo ...19979364557
ivermectin and moxidectin in two filarial systems: resistance of monanema martini; inhibition of litomosoides sigmodontis insemination.effects of ivermectin and moxidectin were compared on two filarial species: monanema martini which presents dermal microfilariae and induces onchocerca-like lesions in its natural murid host lemniscomys striatus, and litomosoides sigmodontis (= l. carinii). m. martini microfilariae showed an unusual resistance to ivermectin, in vitro and in vivo; moxidectin was no more efficient. however, the two drugs used at high concentrations deeply altered the uterine embryogenesis, but had no lethal effect ...19979419842
early reduction of the challenge recovery rate following immunization with irradiated infective larvae in a filaria mouse system.the filaria litomosoides sigmodontis, which develops a patent infection in balb/c mice, was used to determine the fate of a challenge inoculum following immunization of mice with irradiation attenuated infective larvae (3 subcutaneous inoculations at weekly intervals with 25 l3 irradiated at 60 krad, and challenge with 25 l3 two weeks after the final immunization). the adult worm burden of vaccinated mice was reduced to 50% of that of controls although the pattern of larval migration and microfi ...19979438473
the xid defect imparts susceptibility to experimental murine filariosis--association with a lack of antibody and il-10 production by b cells in response to phosphorylcholine.the pathways conferring immunity to filarial infections are not well known, in part because human pathogenic filariae do not develop a full infection cycle in laboratory mice. using the permissive infection with litomosoides sigmodontis in balb/c mice, we have shown previously that worm development is controlled by cd4+ t cells and is inversely correlated with th2 cytokine production. here we analyzed the impact of the xid immunodeficiency on murine filariosis, comparing the course of infection ...19989488152
juvenile female litomosoides sigmodontis produce an excretory/secretory antigen (juv-p120) highly modified with dimethylaminoethanol.a 120 kda antigen produced by juvenile female litomosoides sigmodontis (juv-p120) was isolated and purified. the amino acid composition of the molecule was determined. juv-p120 was shown to be highly modified with n,n-dimethyl-aminoethanol (28.4 mol%). treatment of juv-p120 with potassium hydroxide (beta-elimination) or with sodium m-periodate leads to the destruction of epitopes recognized by antibodies immune affinity-purified with isolated juv-p120. juvenile l. sigmodontis were shown to relea ...19989774792
tetracycline therapy targets intracellular bacteria in the filarial nematode litomosoides sigmodontis and results in filarial infertility.intracellular bacteria have been described in several species of filarial nematodes, but their relationships with, and effects on, their nematode hosts have not previously been elucidated. in this study, intracellular bacteria were observed in tissues of the rodent parasite litomosoides sigmodontis by transmission electron microscopy and by immunohistochemistry using antiendobacterial heat shock protein-60 antisera. molecular phylogenetic analysis of the bacterial 16s ribosomal rna gene, isolate ...19999884329
litomosoides sigmodontis: dynamics of the survival of microfilariae in resistant and susceptible strains of mice.litomosoides sigmodontis in the balb/c mouse is the only model of filariasis which allows the observation of the complete development in an immunocompetent mouse. in this study, we injected microfilariae (mf) intravenously, as well as into the pleural cavity, the site of natural release of mf from adult female worms, and followed the kinetics of elimination within the host. in susceptible balb/c mice, mf circulated at high levels in the blood. in contrast, in c57bl/6 mice, which are refractory t ...200010673342
the wuchereria bancrofti orthologue of brugia malayi sxp1 and the diagnosis of bancroftian filariasis.the gene encoding the wuchereria bancrofti orthologue of the brugia malayi-derived diagnostic antigen sxp1 was identified from a w. bancrofti l3 cdna library and characterized. the wb-sxp-1 cdna encoded a basic protein with a calculated molecular mass of 20.8 kda. wb-sxp-1 was 85% identical to the sxp1 protein described from b. malayi (bm-sxp-1). the wb-sxp-1 sequence also showed significant identity with proteins described from b. pahangi, onchocerca volvulus, acanthochilonema vitea, ascaris su ...200010717303
interleukin-5 is essential for vaccine-mediated immunity but not innate resistance to a filarial parasite.the study of protective immune mechanisms effective against filarial nematodes has been hampered by the inability of these important human pathogens to infect laboratory mice. recently, litomosoides sigmodontis, a natural parasite of rats, has been developed as a valuable model for the study of filarial infection. balb/c mice are fully susceptible to infection with l. sigmodontis third-stage larvae and develop patent infection. in contrast, mice on the c57bl background are resistant, and parasit ...200010768938
targeting of wolbachia endobacteria in litomosoides sigmodontis: comparison of tetracyclines with chloramphenicol, macrolides and ciprofloxacin.endobacteria of the genus wolbachia in filarial nematodes are related to rickettsiaceae and can be depleted by tetracycline antibiotics. this depletion blocks female worm development as well as early embryogenesis, in contrast to the currently used microfilaricidal ivermectin which blocks only the last stage of embryogenesis. since targeting wolbachia is becoming an area of research for the treatment of human filariases, it was investigated if antibiotics other than tetracyclines are able to dep ...200010810023
targeting of wolbachia endobacteria in litomosoides sigmodontis: comparison of tetracyclines with chloramphenicol, macrolides and ciprofloxacinendobacteria of the genus wolbachia in filarial nematodes are related to rickettsiaceae and can be depleted by tetracycline antibiotics. this depletion blocks female worm development as well as early embryogenesis, in contrast to the currently used microfilaricidal ivermectin which blocks only the last stage of embryogenesis. since targeting wolbachia is becoming an area of research for the treatment of human filariases, it was investigated if antibiotics other than tetracyclines are able to dep ...200010810024
phosphocholine-containing, zwitterionic glycosphingolipids of adult onchocerca volvulus as highly conserved antigenic structures of parasitic nematodes.human onchocerca volvulus infection sera were found to recognize zwitterionic glycolipids of o. volvulus and to cross-react with those of other parasitic nematodes (ascaris suum, setaria digitata and litomosoides sigmodontis). by the use of an epitope-specific monoclonal antibody, zwitterionic glycolipids of all these nematode species were observed to contain the antigenic determinant phosphocholine. a hyperimmune serum specific for arthro-series glycolipid structures reacted with the various ne ...200010816437
analysis of genes expressed at the infective larval stage validates utility of litomosoides sigmodontis as a murine model for filarial vaccine development.we used an expressed sequence tag approach to analyze genes expressed by the infective larvae of the rodent filarial parasite litomosoides sigmodontis. one hundred fifty two new genes were identified, including several proposed as vaccine candidates in studies with human filarial parasites. our findings have important implications for the use of l. sigmodontis as a model for filarial infection.200010948183
the role of nitric oxide in the innate resistance to microfilariae of litomosoides sigmodontis in mice.nitric oxide (no) has been shown to be an important effector mechanism in the defence against various pathogens, including filariae. the production of no, as well as h2o2, is induced by the th1 cytokine ifn-gamma. therefore, the microfilariae (mf) of filarial nematodes, which are known to elicit the release of ifn-gamma, may be a target of no release. in this study, we found that mf of the filarial species litomosoides sigmodontis were resistant to the attack of h2o2, but vulnerable to no exposu ...200010972846
il-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis.the pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. we have used the only fully permissive infection of mice with filariae, i.e., infection of balb/c mice with the rodent filarial nematode litomosoides sigmodontis. our previous results showed that worm development is inversely correlated with th2 cytokine production and eosinophilia. the scope of the present study was to directly ...200011138639
a phylogenetic analysis of filarial nematodes: comparison with the phylogeny of wolbachia endosymbionts.infection with the endosymbiotic bacteria wolbachia is widespread in filarial nematodes. previous studies have suggested concordance between the phylogeny of wolbachia with that of their nematode hosts. however, there is only one published molecular phylogenetic study of filarial species, based on the 5s rrna gene spacer. the phylogeny proposed by this study is partially incongruent with previous classifications of filarial nematodes, based on morphological characters. furthermore, both traditio ...200111197770
determinants for resistance and susceptibility to microfilaraemia in litomosoides sigmodontis filariasis.filarial infections of humans are chronic diseases. despite an ongoing immune response, adult filariae continuously produce their offspring, the microfilariae (mf), which are able to persist in sufficient numbers to ensure transmission. in this study, host- and parasite-derived factors, which contribute to persistence of mf, were investigated using the filariasis model of litomosoides sigmodontis in mice. different strains of mice were found to differ widely in their capability to eliminate circ ...200111444617
effects of bay 44-4400, a new cyclodepsipeptide, on developing stages of filariae (acanthocheilonema viteae, brugia malayi, litomosoides sigmodontis) in the rodent mastomys coucha.bay 44-4400 was used as a spot on formulation and administered in single doses of 25 and 100 mg/kg to acanthocheilonema viteae, brugia malayi, and litomosoides sigmodontis infected mastomys coucha on various dates during prepatency, aiming to affect third stage larvae, fourth stage larvae or preadult worms. microfilaraemia levels were controlled in comparison to untreated controls until necropsies were performed 100 days p.i. (a. viteae, l. sigmodontis) and 150 days p.i. (b. malayi) to determine ...200111495640
wolbachia in filarial nematodes: evolutionary aspects and implications for the pathogenesis and treatment of filarial diseases.the presence of intracellular bacteria in the body of various species of filarial nematodes, including important parasites such as brugia malayi, dirofilaria immitis, and onchocerca volvulus, was observed as early as the mid-1970s. these bacteria were shown to be transovarially transmitted (from the female worm to the offspring) and to be present in significant amounts in the body of the nematode. as highlighted by their discoverers, the potential importance of these bacteria is fairly obvious: ...200111516587
filaricidal efficacy of anthelmintically active cyclodepsipeptides.pf 1022a, a novel anthelmintically active cyclodepsipeptide, and bay 44-4400, a semisynthetic derivative of pf 1022a were tested for filaricidal efficacy in mastomys coucha infected with litomosoides sigmodontis, acanthocheilonema viteae and brugia malayi. the parent compound pf 1022a showed limited anti-filarial efficacy in l. sigmodontis and b. malayi infected animals. oral doses of 5 x 100 mg/kg on consecutive days caused only a temporary decrease of microfilariaemia levels. by contrast, bay ...200111595239
litomosoides sigmodontis cystatin acts as an immunomodulator during experimental filariasis.during chronic filariasis, parasite-specific cellular responsiveness is profoundly down-regulated. cystatins, a group of cysteine protease inhibitors, have been implicated in this suppressive activity. in an attempt to investigate the effects of cystatins in vivo, we isolated and expressed a 14 kda protein of the rodent filaria litomosoides sigmodontis with substantial homologies to cystatins from human pathogenic filariae. cystatin was detected in antigen preparations of several developmental s ...200211812494
cloning and expression analysis of two mucin-like genes encoding microfilarial sheath surface proteins of the parasitic nematodes brugia and litomosoides.in several filarial genera the first stage larvae (microfilariae) are enclosed by an eggshell-derived sheath that provides a major interface between the parasite and the host immune system. analysis of the polypeptide constituents of the microfilarial sheath from the cotton rat filaria litomosoides sigmodontis identified two abundant surface glycoproteins: shp3a and shp3. the corresponding genes and the orthologues of the human parasite brugia malayi and the rodent filaria brugia pahangi were cl ...200212356773
real-time pcr for quantification of the bacterial endosymbionts (wolbachia) of filarial nematodes.filarial nematodes harbour intracellular symbiotic bacteria belonging to the genus wolbachia. wolbachia is thought to play an important role in the biology of the nematode. moreover, wolbachia appears to be involved in the immunopathogenesis of filariasis and in the onset of the side-effects of antifilarial therapy. investigations in these research areas require reliable methods to quantify wolbachia both in nematodes and in vertebrate tissues. to this purpose, we designed a quantitative real-ti ...200112402526
involvement of toll-like receptor 4 in the embryogenesis of the rodent filaria litomosoides sigmodontis.to examine the role that lipopolysaccharide (lps)-like molecules from the filarial intracellular endobacteria wolbachia might play in the development of filarial infections, a natural infection in the lps-nonresponsive c3h/hej mouse strain was compared to that of the lps-responsive c3h/hen mouse strain. c3h/hen mice have been shown to be susceptible to the rodent filarial nematode litomosoides sigmodontis, with the development of adult worms including females containing mature microfilariae (fir ...200312592564
antibiotic therapy in murine filariasis (litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on wolbachia and filarial viability.the symbiosis of filarial nematodes and rickettsial wolbachia endobacteria has been exploited as a target for antibiotic therapy of filariasis. depletion of wolbachia after tetracycline treatment results in filarial sterility because of interruption of embryogenesis and inhibits larval development and adult worm viability. the aim of this study was to investigate if antibiotic intervention of balb/c mice infected with the rodent filaria litomosoides sigmodontis with rifampicin or the combination ...200312753632
evidence against wolbachia symbiosis in loa loa.background: the majority of filarial nematode species are host to wolbachia bacterial endosymbionts, although a few including acanthocheilonema viteae, onchocerca flexuosa and setaria equina have been shown to be free of infection. comparisons of species with and without symbionts can provide important information on the role of wolbachia symbiosis in the biology of the nematode hosts and the contribution of the bacteria to the development of disease. previous studies by electron microscopy and ...200312816546
trans-species transfer of wolbachia: microinjection of wolbachia from litomosoides sigmodontis into acanthocheilonema viteae.intracellular bacteria of the genus wolbachia are found in most filarial nematodes, but are lacking in some species like acanthocheilonema viteae. due to their symbiotic nature and their role in the pathology of filarial infections they are considered to be potential targets for intervention against filarial infections in man. infection of a. viteae (a species which does not naturally carry wolbachia) with wolbachia bacteria could allow comparative studies on the effect of the endobacterium on t ...200312866789
resistance and susceptibility to filarial infection with litomosoides sigmodontis are associated with early differences in parasite development and in localized immune reactions.in order to understand natural resistance to filariasis, we compared litomosoides sigmodontis primary infection of c57bl/6 mice, which eliminate the worms before patency, and balb/c mice, in which worms complete their development and produce microfilariae. our analysis over the first month of infection monitoredmigration of the infective larvae from the lymph nodes to the pleural cavity, where the worms settle. although immune responses from the mouse strains differed from the outset, the durati ...200314638768
most of the response elicited against wolbachia surface protein in filarial nematode infection is due to the infective larval stage.immune responses to the intracellular wolbachia bacteria of filarial nematodes are thought to contribute to the pathologic process of filarial infection. here, we compare antibody responses of subjects living in an area where lymphatic filariasis is endemic with antibody responses elicited in a murine model of filarial infection, to provide evidence that the infective larval stage (l3), not adult nematodes, are the primary inducer of responses against wolbachia. in human subjects, antibody respo ...200414702162
the antifilarial activity of a marine red alga, botryocladia leptopoda, against experimental infections with animal and human filariae.the antifilarial activity of the marine red alga botryocladia leptopoda against rodent and human lymphatic filarial parasites is described. the animal filarial species included litomosoides sigmodontis and acanthocheilonema viteae maintained in cotton rats and mastomys coucha, respectively, while a subperiodic strain of the human lymphatic filarial parasite brugia malayi was maintained in m. coucha. the crude extract and its hexane fraction brought about a marked reduction in the peripheral micr ...200415243801
interleukin-10 (il-10) counterregulates il-4-dependent effector mechanisms in murine filariasis.interleukin-10 (il-10) was at first described as a th2-associated cytokine, although more recent reports have shown that immunosuppression applies to both th1 and th2 cell responses, e.g., when produced by t regulatory cells. this concept when applied to human filariasis would argue that high parasite loads are associated with il-10, while bona fide th2 responses, mediated by il-4, il-5, and il-13, are associated with parasite containment. to prove this relationship in a causal manner, we invest ...200415501755
chitinase and fizz family members are a generalized feature of nematode infection with selective upregulation of ym1 and fizz1 by antigen-presenting cells.ym1 and fizz1 are secreted proteins that have been identified in a variety of th2-mediated inflammatory settings. we originally found ym1 and fizz1 as highly expressed macrophage genes in a brugia malayi infection model. here, we show that their expression is a generalized feature of nematode infection and that they are induced at the site of infection with both the tissue nematode litomosoides sigmodontis and the gastrointestinal nematode nippostrongylus brasiliensis. at the sites of infection ...200515618176
malaria-filaria coinfection in mice makes malarial disease more severe unless filarial infection achieves patency.coinfections are common in natural populations, and the literature suggests that helminth coinfection readily affects how the immune system manages malaria. for example, type 1-dependent control of malaria parasitemia might be impaired by the type 2 milieu of preexisting helminth infection. alternatively, immunomodulatory effects of helminths might affect the likelihood of malarial immunopathology. using rodent models of lymphatic filariasis (litomosoides sigmodontis) and noncerebral malaria (cl ...200415633101
removal of regulatory t cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo.human filarial parasites cause chronic infection associated with long-term down-regulation of the host's immune response. we show here that cd4+ t cell regulation is the main determinant of parasite survival. in a laboratory model of infection, using litomosoides sigmodontis in balb/c mice, parasites establish for >60 days in the thoracic cavity. during infection, cd4+ t cells at this site express increasing levels of cd25, ctla-4, and glucocorticoid-induced tnf receptor family-related gene (git ...200515814720
quantitative appraisal of murine filariasis confirms host strain differences but reveals that balb/c females are more susceptible than males to litomosoides sigmodontis.litomosoides sigmodontis, a rodent filarial nematode, can infect inbred laboratory mice, with full development to patency in the balb/c strain. strains such as c57bl/6 are considered resistant, because although filarial development can occur, circulating microfilariae are never detected. this model system has, for the first time, allowed the power of murine immunology to be applied to fundamental questions regarding susceptibility to filarial nematode infection. as this is a relatively new model ...200515820154
blood-feeding in the young adult filarial worms litomosoides sigmodontis.in this study with the filarial model litomosoides sigmodontis, we demonstrate that the worms ingest host red blood cells at a precise moment of their life-cycle, immediately after the fourth moult. the red blood cells (rbc) were identified microscopically in live worms immobilized in pbs at 4 degrees c, and their density assessed. two hosts were used: mongolian gerbils, where microfilaraemia is high, and susceptible balb/c mice with lower microfilaraemia. gerbils were studied at 12 time-points, ...200515830816
the subcutaneous movements of filarial infective larvae are impaired in vaccinated hosts in comparison to primary infected hosts.our aim in this study was to observe the movements of filarial infective larvae following inoculation into the mammalian host and to assess the effect of vaccination on larval migration, in situ. here we present recordings of larvae progressing through the subcutaneous tissues and inguinal lymph node of primary infected or vaccinated mice. we used the filaria litomosoides sigmodontis in balb/c mice that were necropsied 6 hours after the challenge inoculation of 200 larvae. subcutaneous tissue se ...200515916708
co-infected c57bl/6 mice mount appropriately polarized and compartmentalized cytokine responses to litomosoides sigmodontis and leishmania major but disease progression is altered.this study examines the capacity of the mammalian host to fully compartmentalize the response to infection with type 1 vs. type 2 inducing organisms that infect different sites in the body. for this purpose, c57bl/6 mice were infected with the rodent filarial nematode litomosoides sigmodontis followed by footpad infection with the protozoan parasite leishmania major. in this host, nematode infection is established in the thoracic cavity but no microfilariae circulate in the bloodstream. we utili ...200516149989
rnai mediated silencing of actin expression in adult litomosoides sigmodontis is specific, persistent and results in a phenotype.in this report, the actin gene from the rodent filaria litomosoides sigmodontis was successfully knocked down by rna interference (rnai). by establishing controls for measuring off-target rnai effects we showed that lower concentrations of double stranded rna (dsrna) are more effective than those previously reported. while all tested concentrations reduced ls-act transcription, the concentration that consistently reduced ls-act expression to <10% of the controls was 3.5 microm, a 10-fold lower c ...200616546192
differential display of genes expressed in the filarial nematode litomosoides sigmodontis reveals a putative phosphate permease up-regulated after depletion of wolbachia endobacteria.mutualist symbiotic wolbachia endobacteria are found in most filarial nematodes. wolbachia are essential for embryogenesis and for larval development into adults, and thus represent a new target for anti-filarial drug development. tetracycline antibiotics deplete wolbachia in animal model filaria litomosoides sigmodontis and brugia pahangi, as well as in the human parasites brugia malayi, onchocerca volvulus and wuchereria bancrofti. very little is known about the molecular details of the symbio ...200616616613
f4/80+ alternatively activated macrophages control cd4+ t cell hyporesponsiveness at sites peripheral to filarial infection.both t cells and apc have been strongly implicated in the immune suppression observed during filarial nematode infections, but their relative roles are poorly understood, particularly in regard to timing and locality of action. using litomosoides sigmodontis infection of susceptible balb/c mice, we have studied the progression of filarial immunosuppression leading to patent infection with blood microfilaremia. patent infection is associated with decreased immune responsiveness in the draining th ...200616709852
vaccination against filarial nematodes with irradiated larvae provides long-term protection against the third larval stage but not against subsequent life cycle stages.sustainable control of human filariasis would benefit enormously from the development of an effective vaccine. the ability to vaccinate experimental animals, with reductions in worm burden of over 70%, suggests this aim is possible. however, in experimental vaccinations the challenge is usually administered 2 weeks after the immunisation phase and thus the protection obtained is likely to be biased by persisting inflammation. using the murine model litomosoides sigmodontis, we increased the time ...200616765354
lack of eosinophil peroxidase or major basic protein impairs defense against murine filarial infection.eosinophils are a hallmark of allergic diseases and helminth infection, yet direct evidence for killing of helminth parasites by their toxic granule products exists only in vitro. we investigated the in vivo roles of the eosinophil granule proteins eosinophil peroxidase (epo) and major basic protein 1 (mbp) during infection with the rodent filaria litomosoides sigmodontis. mice deficient for either epo or mbp on the 129/svj background developed significantly higher worm burdens than wild-type mi ...200616926417
ultrasonography in filaria-infected rodents: detection of adult litomosoides sigmodontis and brugia malayi filariae.to evaluate the usefulness of ultrasonography (usg) in the detection of adult filariae in rodents. wuchereria bancrofti are frequently detected using usg in humans, whereas adult brugia malayi have not been so far.200616930260
ctla-4 and cd4+ cd25+ regulatory t cells inhibit protective immunity to filarial parasites in vivo.the t cell coinhibitory receptor ctla-4 has been implicated in the down-regulation of t cell function that is a quintessential feature of chronic human filarial infections. in a laboratory model of filariasis, litomosoides sigmodontis infection of susceptible balb/c mice, we have previously shown that susceptibility is linked both to a cd4+ cd25+ regulatory t (treg) cell response, and to the development of hyporesponsive cd4+ t cells at the infection site, the pleural cavity. we now provide evid ...200717878360
does litomosoides sigmodontis synthesize dimethylethanolamine from choline?juvenile female litomosoides sigmodontis secrete a protein (juv-p120) highly modified with dimethylethanolamine (dmae). in an attempt to establish the source of this decoration worms were pulsed with [3h]-choline and [3h]-ethanolamine and the radio-isotope labelled products analysed. both isotope labels were successfully taken up by the worms, as demonstrated by labelling of phospholipids with [3h]-choline, being predominantly incorporated into phosphatidylcholine and [3h]-ethanolamine into phos ...200817892618
litomosoides sigmodontis: vaccine-induced immune responses against wolbachia surface protein can enhance the survival of filarial nematodes during primary infection.wolbachia are bacteria present within the tissues of most filarial nematodes. filarial nematode survival is known to be affected by immune responses generated during filarial nematode infection and immune responses to wolbachia can be found in different species harbouring filarial nematode infections, including humans. using the rodent filarial model litomosoides sigmodontis, we show that pre-exposure to wolbachia surface protein in a th1 context (but not in a th2-context) enhances worm survival ...200817919582
helminth infection with litomosoides sigmodontis induces regulatory t cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model.numerous epidemiological studies have shown an inverse correlation between helminth infections and the manifestation of atopic diseases, yet the immunological mechanisms governing this phenomenon are indistinct. we therefore investigated the effects of infection with the filarial parasite litomosoides sigmodontis on allergen-induced immune reactions and airway disease in a murine model of asthma. infection with l. sigmodontis suppressed all aspects of the asthmatic phenotype: ag-specific ig prod ...200818209076
microfilariae of the filarial nematode litomosoides sigmodontis exacerbate the course of lipopolysaccharide-induced sepsis in mice.helminths facilitate their own survival by actively modulating the immune systems of their hosts. we investigated the impacts that different life cycle stages of the rodent filaria litomosoides sigmodontis have on the inflammatory responses of mice injected with sublethal doses of lipopolysaccharide (lps). mice infected with female adult worms from prepatent infections, worms which have not yet started to release microfilariae, developed lower levels of proinflammatory cytokines in the periphera ...200818250172
infection of the intermediate mite host with wolbachia-depleted litomosoides sigmodontis microfilariae: impaired l1 to l3 development and subsequent sex-ratio distortion in adult worms.the rodent filaria litomosoides sigmodontis harbour wolbachia, endosymbionts essential for worm embryogenesis, larval development and adult survival. to study the effect of tetracycline, which depletes wolbachia, on the development of microfilariae (l1s, mf) to l3 in the intermediate host ornithonyssus bacoti, and to observe the development of wolbachia-depleted l3s in mongolian gerbils (meriones unguiculatus); microfilaremic gerbils were treated orally with tetracycline for 6 weeks (primary inf ...200818282572
pleural cellular reaction to the filarial infection litomosoides sigmodontis is determined by the moulting process, the worm alteration, and the host strain.the filarial nematode litomosoides sigmodontis model was used to decipher the complex in vivo relationships between filariae, granulomas and leukocytes in the host's pleural cavity. the study was performed from d5 p.i.: to d47 p.i. in resistant c57bl/6 mice, to d74 p.i. in susceptible balb/c mice, and to d420 p.i. in permissive jirds. we showed that, during the first month, leukocytes only clustered as granulomas around shed cuticles (exuviae) and with eosinophils as the major constituents. in a ...200818295534
of mice, cattle, and humans: the immunology and treatment of river blindness.river blindness is a seriously debilitating disease caused by the filarial parasite onchocerca volvulus, which infects millions in africa as well as in south and central america. research has been hampered by a lack of good animal models, as the parasite can only develop fully in humans and some primates. this review highlights the development of two animal model systems that have allowed significant advances in recent years and hold promise for the future. experimental findings with litomosoide ...200818446236
antifilarial activity of caesalpinia bonducella against experimental filarial infections.lymphatic filariasis is a disabling disease that continues to cripple population in tropical countries. currently available antifilarial drugs are not able to control the disease. therefore, a better antifilarial is urgently required for proper management of the disease. we undertook this study to assess the antifilarial activity of caesalpinia bonducella-seed kernel against rodent filarial parasite in experimental model.200818820361
inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a t helper type 2 shift and induction of foxp3+ regulatory t cells.we sought to determine whether litomosoides sigmodontis, a filarial infection of rodents, protects against type 1 diabetes in non-obese diabetic (nod) mice. six-week-old nod mice were sham-infected or infected with either l3 larvae, adult male worms, or adult female worms. whereas 82% of uninfected nod mice developed diabetes by 25 weeks of age, no l. sigmodontis-infected mice developed disease. although all mice had evidence of ongoing islet cell inflammation by histology, l. sigmodontis-infect ...200919016910
filarial infection induces protection against p. berghei liver stages in mice.chronic helminth infections such as filariasis in human hosts can be life long, since parasites are equipped with a repertoire of immune evasion strategies. in many areas where helminths are prevalent, other infections such as malaria are co-endemic. it is still an ongoing debate, how one parasite alters immune responses against another. to dissect the relationships between two different parasites residing in the same host, we established a murine model of co-infection with the filarial nematode ...200919049828
early recruitment of natural cd4+ foxp3+ treg cells by infective larvae determines the outcome of filarial infection.human helminth infections are synonymous with impaired immune responsiveness indicating suppression of host immunity. using a permissive murine model of filariasis, litomosoides sigmodontis infection of inbred mice, we demonstrate rapid recruitment and increased in vivo proliferation of cd4(+)foxp3(+) treg cells upon exposure to infective l3 larvae. within 7 days post-infection this resulted in an increased percentage of cd4(+)t cells at the infection site expressing foxp3. antibody-mediated dep ...200919089814
litomosoides sigmodontis: a simple method to infect mice with l3 larvae obtained from the pleural space of recently infected jirds (meriones unguiculatus).litomosoides sigmodontis is a filarial nematode that is used as a mouse model for human filarial infections. the life cycle of l. sigmodontis comprises rodents as definitive hosts and tropical rat mites as alternate hosts. here, we describe a method of infecting mice with third stage larvae (l3) extracted from the pleural space of recently infected jirds (meriones unguiculatus). this method enables infection of mice with a known number of l3 larvae without the time-consuming dissection of l3 lar ...200919463816
a putative nuclear growth factor-like globular nematode specific protein.expressed sequence tags (ests) are an effective approach for discovery of novel genes. in the current study, approximately 250 ests of the cattle parasitic nematode setaria digitata were examined and a cdna clone identified whose coding sequence could not be functionally annotated by searching over publicly available genome, protein, est and sts databases. here, we report the extensive characterization of this orf (up) and its homologues using a bioinformatic approach. uncharacterized protein (s ...200919759810
type 2 immune-inducing helminth vaccination maintains protective efficacy in the setting of repeated parasite exposures.animal studies have demonstrated that helminth vaccines which induce type 2 immune responses can be protective. to date, however, such vaccines have not been tested against repeated parasite challenges. since repeated antigenic challenge of patients with allergic disease results in immunologic tolerance, we hypothesized that a helminth vaccine which induces type 2 immune responses may lose its protective efficacy in the setting of repeated parasite exposures (rpes). to test this hypothesis, we e ...201020035827
antibody isotype analysis of malaria-nematode co-infection: problems and solutions associated with cross-reactivity.antibody isotype responses can be useful as indicators of immune bias during infection. in studies of parasite co-infection however, interpretation of immune bias is complicated by the occurrence of cross-reactive antibodies. to confidently attribute shifts in immune bias to the presence of a co-infecting parasite, we suggest practical approaches to account for antibody cross-reactivity. the potential for cross-reactive antibodies to influence disease outcome is also discussed.201020163714
mitochondrial genes for heme-dependent respiratory chain complexes are up-regulated after depletion of wolbachia from filarial nematodes.the filarial nematodes brugia malayi, wuchereria bancrofti and onchocerca volvulus cause elephantiasis or dermatitis and blindness resulting in severe morbidity. annually, 1.3 billion people are at risk of infection. targeting the essential wolbachia endobacteria of filarial nematodes with doxycycline has proven to be an effective therapy resulting in a block in embryogenesis, worm development and macrofilaricidal effects. however, doxycycline is contraindicated for a large portion of the at ris ...201020362581
filaria-induced il-10 suppresses murine cerebral malaria.filarial nematodes achieve long survival in their hosts due to their capacity to modulate immune responses. therefore, immunomodulation by filarial nematodes may alter responses to concomitant infections such as malaria. cerebral malaria (cm), a severe complication of plasmodium falciparum infections, is triggered as a consequence of the immune response developed against malaria parasites. the question arises whether prior infection with helminth parasites is beneficial against cm. in the presen ...201020420933
basophils amplify type 2 immune responses, but do not serve a protective role, during chronic infection of mice with the filarial nematode litomosoides sigmodontis.chronic helminth infections induce a type 2 immune response characterized by eosinophilia, high levels of ige, and increased t cell production of type 2 cytokines. because basophils have been shown to be substantial contributors of il-4 in helminth infections, and because basophils are capable of inducing th2 differentiation of cd4(+) t cells and ige isotype switching in b cells, we hypothesized that basophils function to amplify type 2 immune responses in chronic helminth infection. to test thi ...201021057084
characterization of the dmae-modified juvenile excretory-secretory protein juv-p120 of litomosoides sigmodontis.juv-p120 is an excretory-secretory 160 kda glycoprotein of juvenile female litomosoides sigmodontis and exhibits features typical for mucins. 50% of its molecular mass is attributed to posttranslational modifications with the unusual substituent dimethylaminoethanol (dmae). by that juv-p120 corresponds to the surface proteins of the microfilarial sheath, shp3 and shp3a. the secreted protein consists of 697 amino acids, organized in two different domains of repeat elements separated by a stretch ...201121241743
a novel and divergent role of granzyme a and b in resistance to helminth infection.granzyme (gzm) a and b, proteases of nk cells and t killer cells, mediate cell death, but also cleave extracellular matrices, inactivate intracellular pathogens, and induce cytokines. moreover, macrophages, th2 cells, regulatory t cells, mast cells, and b cells can express gzms. we recently reported gzm induction in human filarial infection. in this study, we show that in rodent filarial infection with litomosoides sigmodontis, worm loads were significantly reduced in gzma × b and gzmb knockout ...201121248253
effects of doxycycline on early infections of dirofilaria immitis in dogs.the antifilarial effects of tetracycline drugs were first demonstrated when they were found to be highly effective against l(3) and l(4) of brugia pahangi and litomosoides sigmodontis in rodent models. tetracyclines are also now known to have activity against microfilariae and adult dirofilaria immitis, but assessment of their activity against larval and juvenile heartworms has not been reported previously. this study assessed the effects of doxycycline administered orally at 10mg/kg twice daily ...201121345592
ccl17 controls mast cells for the defense against filarial larval entry.filarial parasites have to trespass many barriers to successfully settle within their mammalian host, which is equipped with mechanical borders and complex weaponry of an evolved immune system. however, little is known about mechanisms of early local events in filarial infections. in this study, bone marrow-derived dendritic cells not only upregulated activation markers cd40 and cd80 upon in vitro stimulation with filarial extracts, but also secreted ccl17, a chemokine known to be produced upon ...201121398605
Th2 responses to helminth parasites can be therapeutically enhanced by, but are not dependent upon, GITR-GITR ligand costimulation in vivo.The immune suppression that characterizes human helminth infections can hinder the development of protective immunity or help to reduce pathogenic inflammation. Signaling through the T cell costimulator glucocorticoid-induced TNFR-related protein (GITR) counteracts immune downregulation by augmenting effector T cell responses and abrogating suppression by Foxp3(+) regulatory T cells. Thus, superphysiological Ab-mediated GITR costimulation represents a novel therapy for promoting protective immun ...201121705620
over expression of il-10 by macrophages overcomes resistance to murine filariasis.individuals infected with parasitic helminths are able to tolerate the presence of parasites for considerable time without clinical pathology. immunosuppressive responses induced by the filarial parasite are considered responsible for this long-lasting relationship, inuring to the benefit of both parasite and host. in order to directly link il-10 with parasite survival, we infected mice, in which over expression of il-10 was restricted to macrophages under control of the cd68 promoter (macil-10t ...201121959021
nematode-induced interference with the anti-plasmodium cd8(+) t-cell response can be overcome by optimizing antigen administration.malaria is still responsible for up to 1 million deaths per year worldwide, highlighting the need for protective malaria vaccines. helminth infections that are prevalent in malaria endemic areas can modulate immune responses of the host. here we show that strongyloides ratti, a gut-dwelling nematode that causes transient infections, did not change the efficacy of vaccination against plasmodium berghei. an ongoing infection with litomosoides sigmodontis, a tissue-dwelling filaria that induces chr ...201122161305
Pathogenic nematodes suppress humoral responses to third-party antigens in vivo by IL-10-mediated interference with Th cell function.One third of the human population is infected with helminth parasites. To promote their longevity and to limit pathology, helminths have developed several strategies to suppress the immune response of their host. As this immune suppression also acts on unrelated third-party Ags, a preexisting helminth infection may interfere with vaccination efficacy. In this study, we show that natural infection with Litomosoides sigmodontis suppressed the humoral response to thymus-dependent but not to thymus- ...201121900178
nucleic acid transfection and transgenesis in parasitic nematodes.summarytransgenesis is an essential tool for assessing gene function in any organism, and it is especially crucial for parasitic nematodes given the dwindling armamentarium of effective anthelmintics and the consequent need to validate essential molecular targets for new drugs and vaccines. two of the major routes of gene delivery evaluated to date in parasitic nematodes, bombardment with dna-coated microparticles and intragonadal microinjection of dna constructs, draw upon experience with the f ...201121880161
helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires tgf-β.leading hypotheses to explain helminth-mediated protection against autoimmunity postulate that type 2 or regulatory immune responses induced by helminth infections in the host limit pathogenic th1-driven autoimmune responses. we tested these hypotheses by investigating whether infection with the filarial nematode litomosoides sigmodontis prevents diabetes onset in il-4-deficient nod mice and whether depletion or absence of regulatory t cells, il-10, or tgf-β alters helminth-mediated protection. ...201122174447
deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes.filarial nematodes are tissue-dwelling parasites that can be killed by th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. as a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.201223301106
chronic filarial infection provides protection against bacterial sepsis by functionally reprogramming macrophages.helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. to address this, mice were chronically infected with the filarial nematode litomosoides sigmodontis (l.s.) and the outcome of acute systemic inflammation caused by i.p. escherichia coli inject ...201525611587
fitness cost of litomosoides sigmodontis filarial infection in mite vectors; implications of infected haematophagous arthropod excretory products in host-vector interactions.filariae are a leading cause of infections which are responsible for serious dermatological, ocular, and vascular lesions. infective third stage larvae (l3) are transmitted through the bite of a haematophagous vector. litomosoides sigmodontis is a well-established model of filariasis in the mouse, with the vector being the mite ornithonyssus bacoti. the aim of the study was to analyse the filarial infection in mites to determine the consequences of filarial infection in the blood-feeding and the ...201324089685
the secreted triose phosphate isomerase of brugia malayi is required to sustain microfilaria production in vivo.human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. surprisingly, the most abundant secreted protein of adult brugia malayi is triose phosphate isomerase (tpi), a glycolytic enzyme usually associated with th ...201424586152
phylogenomics and analysis of shared genes suggest a single transition to mutualism in wolbachia of nematodes.wolbachia, endosymbiotic bacteria of the order rickettsiales, are widespread in arthropods but also present in nematodes. in arthropods, a and b supergroup wolbachia are generally associated with distortion of host reproduction. in filarial nematodes, including some human parasites, multiple lines of experimental evidence indicate that c and d supergroup wolbachia are essential for the survival of the host, and here the symbiotic relationship is considered mutualistic. the origin of this mutuali ...023960254
repurposing of approved drugs from the human pharmacopoeia to target wolbachia endosymbionts of onchocerciasis and lymphatic filariasis.lymphatic filariasis and onchocerciasis are debilitating diseases caused by parasitic filarial nematodes infecting around 150 million people throughout the tropics with more than 1.5 billion at risk. as with other neglected tropical diseases, classical drug-discovery and development is lacking and a 50 year programme of macrofilaricidal discovery failed to deliver a drug which can be used as a public health tool. recently, antibiotic targeting of filarial wolbachia, an essential bacterial symbio ...201425516838
endothelial cells release soluble factors that support the long-term survival of filarial worms in vitro.the inability to maintain filarial nematodes in long-term in vitro culture greatly limits research into the basic biology of these parasites and hinders in vitro screening of novel anti-filarial agents. in this study, we sought to characterize nutrients that promote the long-term survival of filarial worms in vitro. using microfilariae (mf) obtained from gerbils infected with litomosoides sigmodontis, a filarial parasite of rodents, we found that dulbecco's modified eagle medium (dmem) supplemen ...201627565719
stage-specific proteomes from onchocerca ochengi, sister species of the human river blindness parasite, uncover adaptations to a nodular lifestyle.despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. the etiological agent, onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. the challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. he ...201627226403
a histochemical study of the nras/let-60 activity in filarial nematodes.control and elimination of filarial pathogens is a central focus of major global health efforts directed at parasitic diseases of developing countries. accomplishment of these goals would be markedly enhanced by the enhanced destruction of the adult stage of filariae. the identification of new, more quantitative biomarkers that correlate with mortality or chemotherapeutic damage to adult filariae, would greatly facilitate, for example, the development of new macrofilaricides.201526130134
comparative analysis of the secretome from a model filarial nematode (litomosoides sigmodontis) reveals maximal diversity in gravid female parasites.filarial nematodes (superfamily filarioidea) are responsible for an annual global health burden of ∼6.3 million disability-adjusted life-years, which represents the greatest single component of morbidity attributable to helminths affecting humans. no vaccine exists for the major filarial diseases, lymphatic filariasis and onchocerciasis; in part because research on protective immunity against filariae has been constrained by the inability of the human-parasitic species to complete their lifecycl ...201424958169
immunization with brugia malayi hsp70 protects mice against litomosoides sigmodontis challenge infection.more than 1·5 billion people are at risk of being infected with filarial nematodes worldwide. therapy and control of transmission are mainly based on mass drug distribution. as these drugs have to be administered annually or biannually and might be loosing their efficacy, a vaccine against filariae is an alternative approach to chemotherapy. in the current study, we have analysed the potential of brugia malayi heat shock protein 70 (bmhsp70) as a vaccine candidate in a murine helminth infection. ...201424359133
extracellular onchocerca-derived small rnas in host nodules and blood.micrornas (mirnas), a class of short, non-coding rna can be found in a highly stable, cell-free form in mammalian body fluids. specific mirnas are secreted by parasitic nematodes in exosomes and have been detected in the serum of murine and dog hosts infected with the filarial nematodes litomosoides sigmodontis and dirofilaria immitis, respectively. here we identify extracellular, parasite-derived small rnas associated with onchocerca species infecting cattle and humans.201525623184
exosomes secreted by nematode parasites transfer small rnas to mammalian cells and modulate innate immunity.in mammalian systems rna can move between cells via vesicles. here we demonstrate that the gastrointestinal nematode heligmosomoides polygyrus, which infects mice, secretes vesicles containing micrornas (mirnas) and y rnas as well as a nematode argonaute protein. these vesicles are of intestinal origin and are enriched for homologues of mammalian exosome proteins. administration of the nematode exosomes to mice suppresses type 2 innate responses and eosinophilia induced by the allergen alternari ...201425421927
nod2 dependent neutrophil recruitment is required for early protective immune responses against infectious litomosoides sigmodontis l3 larvae.nucleotide-binding oligomerization domain-containing protein 2 (nod2) recognizes muramyl dipeptide (mdp) of bacterial cell walls, triggering nfκb-induced pro-inflammation. as most human pathogenic filariae contain wolbachia endobacteria that synthesize the mdp-containing cell wall precursor lipid ii, nod2's role during infection with the rodent filaria litomosoides sigmodontis was investigated. in nfκb reporter-cells, worm-extract containing wolbachia induced nod2 and nod1. nod2-deficient mice i ...201628004792
filarial infection or antigen administration improves glucose tolerance in diet-induced obese mice.helminths induce type 2 immune responses and establish an anti-inflammatory milieu in their hosts. this immunomodulation was previously shown to improve diet-induced insulin resistance which is linked to chronic inflammation. in the current study, we demonstrate that infection with the filarial nematode litomosoides sigmodontis increased the eosinophil number and alternatively activated macrophage abundance within epididymal adipose tissue (eat) and improved glucose tolerance in diet-induced obe ...201627544668
fat-associated lymphoid clusters control local igm secretion during pleural infection and lung inflammation.fat-associated lymphoid clusters (falc) are inducible structures that support rapid innate-like b-cell immune responses in the serous cavities. little is known about the physiological cues that activate falcs in the pleural cavity and more generally the mechanisms controlling b-cell activation in falcs. here we show, using separate models of pleural nematode infection with litomosoides sigmodontis and altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity ra ...201627582256
neutropenic mice provide insight into the role of skin-infiltrating neutrophils in the host protective immunity against filarial infective larvae.our knowledge and control of the pathogenesis induced by the filariae remain limited due to experimental obstacles presented by parasitic nematode biology and the lack of selective prophylactic or curative drugs. here we thought to investigate the role of neutrophils in the host innate immune response to the infection caused by the litomosoides sigmodontis murine model of human filariasis using mice harboring a gain-of-function mutation of the chemokine receptor cxcr4 and characterized by a prof ...201627111140
combination of worm antigen and proinsulin prevents type 1 diabetes in nod mice after the onset of insulitis.animal studies demonstrated that administration of helminth products can protect from autoimmune diseases. however, the success of such administrations is limited in the case of type 1 diabetes, as protection is only provided if the administration is started before the development of insulitis. in this study we investigated whether inclusion of helminth antigen administrations to an antigen-specific treatment with proinsulin improves the protective effect by triggering non-specific regulatory im ...201626898311
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