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plasmodium berghei anka (pba) infection of c57bl/6j mice: a model of severe malaria.the term "severe malaria" refers to a wide spectrum of syndromes in plasmodium-infected humans including cerebral malaria (cm), respiratory distress, severe anemia, liver dysfunction, and hypoglycemia. mouse models have been employed to further our understanding of the pathology and immune responses that occur during plasmodium infection. evidence of brain, liver, lung, and spleen pathology, as well as anemia and tissue-sequestration of parasites, has been reported in various strains of inbred m ...201323824903
in vitro and in vivo antimalarial activity and cytotoxicity of extracts, fractions and a substance isolated from the amazonian plant tachia grandiflora (gentianaceae).tachia sp. are used as antimalarials in the amazon region and in vivo antimalarial activity of a tachia sp. has been previously reported. tachia grandiflora maguire and weaver is an amazonian antimalarial plant and herein its cytotoxicity and antimalarial activity were investigated. spectral analysis of the tetraoxygenated xanthone decussatin and the iridoid aglyone amplexine isolated, respectively, from the chloroform fractions of root methanol and leaf ethanol extracts was performed. in vitro ...023827996
the etramp family member sep2 is expressed throughout plasmodium berghei life cycle and is released during sporozoite gliding motility.the early transcribed membrane proteins etramps belong to a family of small, transmembrane molecules unique to plasmodium parasite, which share a signal peptide followed by a short lysine-rich stretch, a transmembrane domain and a variable, highly charged c-terminal region. etramps are usually expressed in a stage-specific manner. in the blood stages they localize to the parasitophorous vacuole membrane and, in described cases, to vesicle-like structures exported to the host erythrocyte cytosol. ...201323840634
il-23 protection against plasmodium berghei infection in mice is partially dependent on il-17 from macrophages.although il-12 is believed to contribute to protective immune responses, the role played by il-23 (a member of the il-12 family) in malaria is elusive. here, we show that il-23 is produced during infection with plasmodium berghei nk65. mice deficient in il-23 (p19ko) had higher parasitemia and died earlier than wild-type (wt) controls. interestingly, p19ko mice had lower numbers of il-17-producing splenic cells than their wt counterparts. furthermore, mice deficient in il-17 (17ko) suffered high ...201323843079
phytochemical screening, antimalarial and histopathological studies of allophylus africanus and tragia benthamii.the anti-malarial potential of different parts of allophylus africanus p. beauv and tragia benthamii baker were determined in vivo for suppressive, curative and cytotoxic activities in mice receiving 0.2 ml of a standard inoculum size of 1 × 10(7) infected erythrocytes of plasmodium berghei (nk-65) intraperitoneally. the a. africanus extracts suppressed parasitaemia following administration to infected mice by 92.82%-97.81% on day 7 post-infection against 96.81% for chloroquine. the infected ext ...201323845545
synthesis and antiprotozoal activity of original porphyrin precursors and derivatives.importance of heme in african trypanosomes, leishmania sp. and plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. consequently, twenty-four porphyrin precursors and derivatives were evaluated against leishmania donovani, trypanosoma brucei and plasmodium sp. the best active compound against trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, wit ...201323851117
irf8-regulated genomic responses drive pathological inflammation during cerebral malaria.interferon regulatory factor 8 (irf8) is required for development, maturation and expression of anti-microbial defenses of myeloid cells. bxh2 mice harbor a severely hypomorphic allele at irf8 (irf8(r294c)) that causes susceptibility to infection with intracellular pathogens including mycobacterium tuberculosis. we report that bxh2 are completely resistant to the development of cerebral malaria (ecm) following plasmodium berghei anka infection. comparative transcriptional profiling of brain rna ...201323853600
improved efficacy of fosmidomycin against plasmodium and mycobacterium species by combination with the cell-penetrating peptide octaarginine.cellular drug delivery can improve efficacy and render intracellular pathogens susceptible to compounds that cannot permeate cells. the transport of physiologically active compounds across membranes into target cells can be facilitated by cell-penetrating peptides (cpps), such as oligoarginines. here, we investigated whether intracellular delivery of the drug fosmidomycin can be improved by combination with the cpp octaarginine. fosmidomycin is an antibiotic that inhibits the second reaction in ...201323856773
age-related cd4(+)cd25(+)foxp3(+) regulatory t-cell responses during plasmodium berghei anka infection in mice susceptible or resistant to cerebral malaria.different functions have been attributed to cd4(+)cd25(+)foxp3(+) regulatory t-cells (tregs) during malaria infection. herein, we describe the disparity in treg response and pro- and anti-inflammatory cytokines during infection with plasmodium berghei anka between young (3-week-old) and middle-aged (8-month-old) c57bl/6 mice. young mice were susceptible to cerebral malaria (cm), while the middle-aged mice were resistant to cm and succumbed to hyperparasitemia and severe anemia. the levels of pro ...201323864739
the plasmodium translocon of exported proteins (ptex) component thioredoxin-2 is important for maintaining normal blood-stage growth.plasmodium parasites remodel their vertebrate host cells by translocating hundreds of proteins across an encasing membrane into the host cell cytosol via a putative export machinery termed ptex. previously ptex150, hsp101 and exp2 have been shown to be bona fide members of ptex. here we validate that ptex88 and trx2 are also genuine members of ptex and provide evidence that expression of ptex components are also expressed in early gametocytes, mosquito and liver stages, consistent with observati ...201323869529
glutathione peroxidase contributes with heme oxygenase-1 to redox balance in mouse brain during the course of cerebral malaria.oxidative stress has been attributed both a key pathogenic and rescuing role in cerebral malaria (cm). in a plasmodium berghei anka murine model of cm, host redox signaling and functioning were examined during the course of neurological damage. host antioxidant defenses were early altered at the transcriptional level indicated by the gradually diminished expression of superoxide dismutase-1 (sod-1), sod-2, sod-3 and catalase genes. during severe disease, this led to the dysfunctional activity of ...201323872112
immunisation against a serine protease inhibitor reduces intensity of plasmodium berghei infection in mosquitoes.the mosquito innate immune response is able to clear the majority of plasmodium parasites. this immune clearance is controlled by a number of regulatory molecules including serine protease inhibitors (serpins). to determine whether such molecules could represent a novel target for a malaria transmission-blocking vaccine, we vaccinated mice with anopheles gambiae serpin-2. antibodies against anopheles gambiae serpin-2 significantly reduced the infection of a heterologous anopheles species (anophe ...201323872520
antimalarial, hematological, and antioxidant effects of methanolic extract of terminalia avicennioides in plasmodium berghei-infected mice.terminalia avicennioides guill. & perr. (combretaceae) is used traditionally to treat malaria in nigeria. to establish its efficacy, methanolic extract of t. avicennioides bark was investigated for antimalarial activity against plasmodium berghei (nk-65) in mice. twenty-five mice in five groups were used for this study. group 1 was uninfected normal control. twenty mice infected with p. berghei were grouped as untreated negative control (group 2), 5 mg/kg b.w. p.o. artesunate-treated positive co ...201323873616
in vitro and in vivo antimalarial activity and cytotoxicity of extracts and fractions from the leaves, root-bark and stem-bark of triclisia gilletii.to evaluate the in vitro antiplasmodial activity and cytotoxicity, and the in vivo activity of extracts and fractions from the leaves, root-bark and stem-bark of triclisia gilletii (de wild) staner (menispermaceae), used in traditional medicine against malaria.201323876596
mitochondrial inactivation by anopheles albimanus cecropin 3: molecular mechanisms.cecropin 3 (ccrp3) is an antimicrobial peptide from anopheles albimanus, which is expressed during plasmodium berghei infection. here, we report that synthetic ccrp3, aside from antibacterial activity, also shows cardio regulatory functions. in rats, ccrp3 significantly diminishes blood pressure as well as the heartbeat frequency at nanomolar concentration. ccrp3 affect the rat cardiac muscle mitochondria, inducing uncoupling of oxidative phosphorylation, oxygen consumption and transport of ca(2 ...201423880546
evaluation of novel lipid based formulation of β-artemether and lumefantrine in murine malaria model.the present investigation aims at formulating lipid based drug delivery system of β-artemether and lumefantrine and comparative pharmacological evaluation with innovator formulation. commercial modified oil and indigenous natural fatty acids comprised the oily phase in developing lipidic formulation of β-artemether and lumefantrine. the developed system was characterized for mean globule size, stability by freeze thaw cycles, and birefringence. developed formulation and innovator formulation wer ...201323886650
the role of hemocytes in anopheles gambiae antiplasmodial immunity.hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. the effect of activating toll signaling in hemocytes on plasmodium survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor cactus was silenced. these transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the ...201323886925
nanoparticle formulations of decoquinate increase antimalarial efficacy against liver stage plasmodium infections in mice.decoquinate has potent activity against both plasmodium hepatic development and red cell replication when tested in vitro. decoquinate, however, is practically insoluble in water. to achieve its maximal in vivo efficacy, we generated nanoparticle formulations of decoquinate with a mean particle size less than 400 nm. three separate preparations at doses of decoquinate 0.5-5 mg/kg were examined in mice infected with plasmodium berghei. oral administration of nanoparticle decoquinate at a dose of ...201423891618
role of il-10-producing regulatory b cells in control of cerebral malaria in plasmodium berghei infected mice.cerebral malaria (cm) is a neurological syndrome often occurring in severe malaria. although cm is known as an immunopathology in brain tissue mediated by excessive proinflammatory cytokines, the immunoregulatory mechanism is poorly understood. here, we investigated the role of il-10-producing regulatory b (breg) cells in modulating cm development in a murine model of plasmodium berghei anka infection. we observed that blood-stage p. berghei induced expansion of il-10-producing breg cells in c57 ...201323893352
cd8+ t cells specific for a malaria cytoplasmic antigen form clusters around infected hepatocytes and are protective at the liver stage of infection.following anopheles mosquito-mediated introduction into a human host, plasmodium parasites infect hepatocytes and undergo intensive replication. accumulating evidence indicates that cd8(+) t cells induced by immunization with attenuated plasmodium sporozoites can confer sterile immunity at the liver stage of infection; however, the mechanisms underlying this protection are not clearly understood. to address this, we generated recombinant plasmodium berghei anka expressing a fusion protein of an ...201323897612
development of severe pathology in immunized pregnant mice challenged with lethal malaria parasites.pregnant women are highly susceptible to malaria infection because of their low immunity and are at increased risk of maternal illness or death, in addition to spontaneous abortion, stillbirth, premature delivery, and low birth weight. however, the detailed pathogenesis of maternal malaria remains unclear. in this study, we evaluated a mouse model that shows similar severe pathological features of pregnant women during plasmodium falciparum infection and investigated the pathogenesis of maternal ...201323897619
a novel chitosan based antimalarial drug delivery against plasmodium berghei infection.chitosan is a natural polysaccharide that has attracted significant scientific interest during the last two decades and chitosan based nanodrug delivery systems seem to be a hopeful and viable strategy for improving disease treatment. this study aims to evaluate the potency of the polymer based nanochloroquine in application for attenuation of plasmodium berghei infection in swiss mice and effectiveness against the parasite induced oxidative stress and deoxyribo nucleic acid (dna) damage in lymp ...201323906613
the c-type lectin receptor dcir is crucial for the development of experimental cerebral malaria.cerebral malaria (cm) is the most severe complication of malaria. the murine plasmodium berghei anka (pba) infection model has helped to identify crucial players in the pathogenesis of cm. however, the role of pattern recognition receptors in innate immunity to cm induction is still poorly understood. c-type lectin receptors (clrs) represent a family of pattern recognition receptors that recognize carbohydrate structures on pathogens and self-ags often in a ca(2+)-dependent manner. in this study ...201323918990
plasmodium products contribute to severe malarial anemia by inhibiting erythropoietin-induced proliferation of erythroid precursors.low reticulocytosis, indicating reduced red blood cell (rbc) output, is an important feature of severe malarial anemia. evidence supports a role for plasmodium products, especially hemozoin (hz), in suppressed erythropoiesis during malaria, but the mechanism(s) involved remains unclear. here, we demonstrated that low reticulocytosis and suppressed erythropoietin (epo)-induced erythropoiesis are features of malarial anemia in plasmodium yoelii- and plasmodium berghei anka-infected mice, similar t ...201423922378
malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.heme metabolism is central to malaria parasite biology. the parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. the parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. to study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (alas), and the last enzyme, ferrochelatase (fc), in the he ...201323935500
cytoadherence of plasmodium berghei-infected red blood cells to murine brain and lung microvascular endothelial cells in vitro.sequestration of infected red blood cells (irbc) within the cerebral and pulmonary microvasculature is a hallmark of human cerebral malaria (hcm). the interaction between irbc and the endothelium in hcm has been studied extensively and is linked to the severity of malaria. experimental cm (ecm) caused by plasmodium berghei anka reproduces most features of hcm, although the sequestration of rbc infected by p. berghei anka (pba-irbc) has not been completely delineated. the role of pba-irbc sequest ...201323940206
antimalarial and safety evaluation of pluchea lanceolata (dc.) oliv. & hiern: in-vitro and in-vivo study.many of the effective therapeutic strategies have been derived from ethnopharmacologically used natural products. pluchea lanceolata is an herb employed in indian folk medicine for malaria like fever but it lacks proper pharmacological intervention.201323954323
metabolite extract of streptomyces hygroscopicus hygroscopicus inhibit the growth of plasmodium berghei through inhibition of ubiquitin - proteasome system.streptomyces hygroscopicus hygroscopicus, a member of family of actinomycetes produces eponemycin a proteasome inhibitor that can inhibit ubiquitin-proteasome system (ups) function in eukaryotic cell. previous study showed that coronamycin, an active substrate isolated from streptomyces sp. can act as anti-plasmodial, antibacterial, and antifungal, however the research did not show the mechanism of coronamycin in inhibiting the growth of plasmodium. this research was done to reveal if eponemycin ...201323959495
identification of piggybac-mediated insertions in plasmodium berghei by next generation sequencing.the piggybac transposon system provides a powerful forward genetics tool to study gene function in plasmodium parasites via random insertion mutagenesis and phenotypic screening. the identification of genotype of piggybac mutants in the plasmodium genome is thus an indispensable step in forward genetic analysis. several pcr-based approaches have been used to identify the piggybac insertion sites in plasmodium falciparum and plasmodium berghei, but all are tedious and inefficient. next generation ...201323961915
cd36 and fyn kinase mediate malaria-induced lung endothelial barrier dysfunction in mice infected with plasmodium berghei.severe malaria can trigger acute lung injury characterized by pulmonary edema resulting from increased endothelial permeability. however, the mechanism through which lung fluid conductance is altered during malaria remains unclear. to define the role that the scavenger receptor cd36 may play in mediating this response, c57bl/6j (wt) and cd36-/- mice were infected with p. berghei anka and monitored for changes in pulmonary endothelial barrier function employing an isolated perfused lung system. w ...201323967147
the curative and prophylactic effects of xylopic acid on plasmodium berghei infection in mice.efforts have been intensified to search for more effective antimalarial agents because of the observed failure of some artemisinin-based combination therapy (act) treatments of malaria in ghana. xylopic acid, a pure compound isolated from the fruits of the xylopia aethiopica, was investigated to establish its attributable prophylactic, curative antimalarial, and antipyretic properties. the antimalarial properties were determined by employing xylopic acid (10-100 mg/kg) in icr mice infected with ...201323970953
targeted mutagenesis in the malaria mosquito using tale nucleases.anopheles gambiae, the main mosquito vector of human malaria, is a challenging organism to manipulate genetically. as a consequence, reverse genetics studies in this disease vector have been largely limited to rna interference experiments. here, we report the targeted disruption of the immunity gene tep1 using transgenic expression of transcription-activator like effector nucleases (talens), and the isolation of several tep1 mutant a. gambiae lines. these mutations inhibited protein production a ...201323977401
anti-erythropoietin antibody levels and its association with anaemia in different strains of semi-immune mice infected with plasmodium berghei anka.malaria anaemia is still a major public health problem and its pathogenesis still unclear. interestingly, the progression of anaemia is at relatively low parasitaemia with some mortality in the semi-immune individuals in the endemic areas despite adequate erythropoietin (epo) synthesis. a recent study has shown that treatment with exogenous anti-erythropoietin (anti-epo) antibodies (ab) of infected mice gives protection against malaria infection, suggesting an important role for anti-epo ab in m ...201323978045
phytochemical analysis and antimalarial activity aqueous extract of lecaniodiscus cupanioides root.root aqueous extract of lecaniodiscus cupanioides was evaluated for antimalarial activity and analyzed for its phytochemical constituents. twenty-four (24) albino mice were infected by intraperitoneal injection of standard inoculum of chloroquine sensitive plasmodium berghei (nk 65). the animals were randomly divided into 6 groups of 3 mice each. group 1 served as the control while groups ii-iv were orally administered 50, 150, and 250 mg/kg body weights of extract. groups 5 and 6 received 1.75 ...201323983718
antimalarial activity of cocos nucifera husk fibre: further studies.in this study, the antimalarial and toxicity potentials of husk fibre extracts of five nigerian varieties of cocos nucifera were evaluated in vitro. the only active extract fraction, west african tall (wat) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25-500 mg/kg body weight) using various organ function indices. the results revealed that wat ethyl acetate extract fraction (wateaef) contained alk ...201323983800
azadirachta indica ethanolic extract protects neurons from apoptosis and mitigates brain swelling in experimental cerebral malaria.cerebral malaria is a rapidly developing encephalopathy caused by the apicomplexan parasite plasmodium falciparum. drugs currently in use are associated with poor outcome in an increasing number of cases and new drugs are urgently needed. the potential of the medicinal plant azadirachta indica (neem) for the treatment of experimental cerebral malaria was evaluated in mice.201323984986
mice lacking inducible nitric oxide synthase develop exacerbated hepatic inflammatory responses induced by plasmodium berghei nk65 infection.infection of mice with plasmodium berghei nk65 represents a well-recognized malaria model in which infection is accompanied by an intense hepatic inflammatory response. enzyme-inducible nitric oxide synthase is an important regulator of inflammation and leukocyte recruitment in microvessels, but these functions have yet to be evaluated in experimental malaria. in this study, we assessed the involvement of inducible nitric oxide synthase in inflammatory responses to murine experimental malaria in ...201323988520
protection of renal function by green tea extract during plasmodium berghei infection.impairment of renal function from oxidative stress during malaria infection is one of the leading causes of death in endemic areas. since blood urea nitrogen and creatinine levels in plasma can be used as markers for monitoring renal damage, this study investigated the effect of green tea extract on reduction of blood urea nitrogen and creatinine levels during malaria infection using plasmodium berghei anka infected mice as in vivo model. for in vivo testing, icr mice were infected with 1 × 10(7 ...201323988625
synthesis and in vitro and in vivo evaluation of antimalarial polyamines.we recently reported that 1,14-diphenylacetamide derivatives of spermine exhibit potent nm in vitro growth inhibition properties of plasmodium falciparum. in an effort to expand the structure-activity relationship of this compound class towards malaria, we have prepared and biologically tested a library that includes benzamide and 3-phenylpropanamide 'capping acid' groups, and polyamines that include spermine (pa3-4-3) and chain extended analogues pa3-8-3 and pa3-12-3. 2-hydroxy and 2,5-dimethox ...201323995215
treatment of pregnant balb/c mice with sulphadoxine pyrimethamine or chloroquine abrogates plasmodium berghei induced placental pathology.malaria infection during pregnancy is a risk factor for foetus survival and is associated with abortion, premature delivery and low birth weight of infants in malaria endemic regions. in these regions, prophylactic measures and treatment mainly rely on chloroquine and sulphadoxine pyrimethamine, but their efficacy in reducing the placental pathology has not been studied. therefore, the present study was designed to assess the effectiveness of chloroquine and sulphadoxine pyrimethamine treatment ...201424013006
expression profiling of plasmodium berghei hsp70 genes for generation of bright red fluorescent parasites.live cell imaging of recombinant malarial parasites encoding fluorescent probes provides critical insights into parasite-host interactions and life cycle progression. in this study, we generated a red fluorescent line of the murine malarial parasite plasmodium berghei. to allow constitutive and abundant expression of the mcherry protein we profiled expression of all members of the p. berghei heat shock protein 70 (hsp70) family. we identified pbhsp70/1, an invariant ortholog of plasmodium falcip ...201324013507
density-dependent blood stage plasmodium falciparum suppresses malaria super-infection in a malaria holoendemic population.recent studies of plasmodium berghei malaria in mice show that high blood-stage parasitemia levels inhibit the development of subsequent liver-stage infections. whether a similar inhibitory effect on liver-stage plasmodium falciparum by blood-stage infection occurs in humans is unknown. we have analyzed data from a treatment-time-to-infection cohort of children < 10 years of age residing in a malaria holoendemic area of kenya where people experience a new blood-stage infection approximately ever ...201324019439
bacteria- and imd pathway-independent immune defenses against plasmodium falciparum in anopheles gambiae.the mosquito anopheles gambiae uses its innate immune system to control bacterial and plasmodium infection of its midgut tissue. the activation of potent imd pathway-mediated anti-plasmodium falciparum defenses is dependent on the presence of the midgut microbiota, which activate this defense system upon parasite infection through a peptidoglycan recognition protein, pgrplc. we employed transcriptomic and reverse genetic analyses to compare the p. falciparum infection-responsive transcriptomes o ...201324019865
an oral malaria therapy: curcumin-loaded lipid-based drug delivery systems combined with β-arteether.curcumin (cc), a potential antimalarial drug, has poor water solubility, stability and oral bioavailability. to circumvent these pitfalls, lipid-based drug delivery systems (lbddss) with a high cc loading (30 mg/g) were formulated. in a biorelevant gastric medium, cc-lbddss formed particle sizes in the range of 30-40 nm. during in vitro lipolysis, 90-95% of the cc remained solubilized, whereas 5-10% of the cc precipitated as an amorphous solid, with a high rate of re-dissolution in a biorelevant ...201324021359
identification of the plasmodium berghei resistance locus 9 linked to survival on chromosome 9.one of the main causes of mortality from severe malaria in plasmodium falciparum infections is cerebral malaria (cm). an important host genetic component determines the susceptibility of an individual to develop cm or to clear the infection and become semi-immune. as such, the identification of genetic loci associated with susceptibility or resistance may serve to modulate disease severity.201324025732
pre-existing schistosoma japonicum infection alters the immune response to plasmodium berghei infection in c57bl/6 mice.since helminths and malaria parasites are often co-endemic, it is important to clarify the immunoregulatory mechanism that occurs during the process of co-infection. a previous study confirmed that dendritic cells (dcs) are involved in the establishment and regulation of the t-cell-mediated immune response to malaria infection. in the current study, distinct response profiles for splenic dcs and regulatory t cell (treg) responses were assessed to evaluate the effects of a pre-existing schistosom ...201324034228
the evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (msp-9), in plasmodium vivax and closely related species.the merozoite surface protein-9 (msp-9) has been considered a target for an anti-malarial vaccine since it is one of many proteins involved in the erythrocyte invasion, a critical step in the parasite life cycle. orthologs encoding this antigen have been found in all known species of plasmodium parasitic to primates. in order to characterize and investigate the extent and maintenance of msp-9 genetic diversity, we analyzed dna sequences of the following malaria parasite species: plasmodium falci ...201324044894
screening of novel malaria dna vaccine candidates using full-length cdna library.no licensed malaria vaccine exists, in spite of intensive development efforts. we have been investigating development of a dna vaccine to prevent malaria infection. to date, we have established a full-length cdna expression library from the erythrocytic-stage murine malaria parasite, plasmodium berghei. we found that immunization of mice with combined 2000 clones significantly prolonged survival after challenge infection and that splenocytes from the immunized mice showed parasite-specific cytok ...201324055215
metabolic profiling framework for discovery of candidate diagnostic markers of malaria.despite immense efforts to combat malaria in tropical and sub-tropical regions, the potency of this vector-borne disease and its status as a major driver of morbidity and mortality remain undisputed. we develop an analytical pipeline for characterizing plasmodium infection in a mouse model and identify candidate urinary biomarkers that may present alternatives to immune-based diagnostic tools. we employ (1)h nuclear magnetic resonance (nmr) profiling followed by multivariate modeling to discover ...201324067624
a nondiscriminating glutamyl-trna synthetase in the plasmodium apicoplast: the first enzyme in an indirect aminoacylation pathway.the malaria parasite plasmodium falciparum and related organisms possess a relict plastid known as the apicoplast. apicoplast protein synthesis is a validated drug target in malaria because antibiotics that inhibit translation in prokaryotes also inhibit apicoplast protein synthesis and are sometimes used for malaria prophylaxis or treatment. we identified components of an indirect aminoacylation pathway for gln-trna(gln) biosynthesis in plasmodium that we hypothesized would be essential for api ...201324072705
two putative protein export regulators promote plasmodium blood stage development in vivo.protein export is considered an essential feature of malaria parasite blood stage development. here, we examined five components of the candidate plasmodium translocon of exported proteins (ptex), a complex thought to mediate protein export across the parasitophorous vacuole membrane into the host cell. using the murine malaria model parasite plasmodium berghei, we succeeded in generating parasite lines lacking ptex88 and thioredoxin 2 (trx2). repeated attempts to delete the remaining three tran ...201324076174
imaging plasmodium immunobiology in the liver, brain, and lung.plasmodium falciparum malaria is responsible for the deaths of over half a million african children annually. until a decade ago, dynamic analysis of the malaria parasite was limited to in vitro systems with the typical limitations associated with 2d monocultures or entirely artificial surfaces. due to extremely low parasite densities, the liver was considered a black box in terms of plasmodium sporozoite invasion, liver stage development, and merozoite release into the blood. further, nothing w ...201424076429
the transcription factor t-bet regulates parasitemia and promotes pathogenesis during plasmodium berghei anka murine malaria.the pathogenesis of experimental cerebral malaria (ecm) is an immunologic process, mediated in part by th1 cd4(+) t cells. however, the role of the th1 cd4(+) t cell differentiation program on the ability to control parasitemia and susceptibility to ecm disease during blood stage malaria has never been assessed directly. using the plasmodium berghei anka murine model of ecm and mice deficient for the transcription factor t-bet (the master regulator of th1 cells) on the susceptible c57bl/6 backgr ...201324078698
comparative susceptibility of different biological forms of anopheles stephensi to plasmodium berghei anka strain.there are varying degrees of compatibility between malaria parasite-mosquito species, and understanding this compatibility may be crucial for developing effective transmission-blocking vaccines. this study investigates the compatibility of different biological forms of a malaria vector, anopheles stephensi, to plasmodium berghei anka strain.201324086525
a purine analog synergizes with chloroquine (cq) by targeting plasmodium falciparum hsp90 (pfhsp90).drug resistance, absence of an effective vaccine, and inadequate public health measures are major impediments to controlling plasmodium falciparum malaria worldwide. the development of antimalarials to which resistance is less likely is paramount. to this end, we have exploited the chaperone function of p. falciparum hsp90 (pfhsp90) that serves to facilitate the expression of resistance determinants.201324098696
structure-activity-relationship studies around the 2-amino group and pyridine core of antimalarial 3,5-diarylaminopyridines lead to a novel series of pyrazine analogues with oral in vivo activity.replacement of the pyridine core of antimalarial 3,5-diaryl-2-aminopyridines led to the identification of a novel series of pyrazine analogues with potent oral antimalarial activity. however, other changes to the pyridine core and replacement or substitution of the 2-amino group led to loss of antimalarial activity. the 3,5-diaryl-2-aminopyrazine series showed impressive in vitro antiplasmodial activity against the k1 (multidrug resistant) and nf54 (sensitive) strains of plasmodium falciparum in ...201324099149
il-27 receptor signaling regulates memory cd4+ t cell populations and suppresses rapid inflammatory responses during secondary malaria infection.interleukin-27 (il-27) is known to control primary cd4(+) t cell responses during a variety of different infections, but its role in regulating memory cd4(+) t responses has not been investigated in any model. in this study, we have examined the functional importance of il-27 receptor (il-27r) signaling in regulating the formation and maintenance of memory cd4(+) t cells following malaria infection and in controlling their subsequent reactivation during secondary parasite challenge. we demonstra ...201424101691
anti-plasmodial activity of some zulu medicinal plants and of some triterpenes isolated from them.mimusops caffra e. mey. ex a.dc and mimusops obtusifolia lam (both members of the sapotaceae family), and hypoxis colchicifolia bak (family hypoxidaceae) are used by traditional healers in zululand to manage malaria. anti-plasmodial investigation of the crude extracts and some triterpenes isolated from the plants showed activity against a chloroquine sensitive (cqs) strain of plasmodium falciparum (d10). among the crude extracts the leaves of m. caffra exhibited the highest activity, with an ic₅ ...201324108397
tlr4 ligand formulation causes distinct effects on antigen-specific cell-mediated and humoral immune responses.the formulation of tlr ligands and other immunomodulators has a critical effect on their vaccine adjuvant activity. in this work, the synthetic tlr4 ligand gla was formulated with three distinct vaccine delivery system platforms (aqueous suspension, liposome, or oil-in-water emulsion). the effect of the different formulations on the adaptive immune response to protein subunit vaccines was evaluated in the context of a recombinant malaria antigen, plasmodium berghei circumsporozoite protein (pbcs ...201324120675
computational and experimental analysis identified 6-diazo-5-oxonorleucine as a potential agent for treating infection by plasmodium falciparum.plasmodium falciparum (pf) is the most severe malaria parasite. it is developing resistance quickly to existing drugs making it indispensable to discover new drugs. effective drugs have been discovered targeting metabolic enzymes of the parasite. in order to predict new drug targets, computational methods can be used employing database information of metabolism. using this data, we performed recently a computational network analysis of metabolism of pf. we analyzed the topology of the network to ...201324121016
flavones as isosteres of 4(1h)-quinolones: discovery of ligand efficient and dual stage antimalarial lead compounds.malaria is responsible for nearly one million deaths annually, and the increasing prevalence of multi-resistant strains of plasmodium falciparum poses a great challenge to controlling the disease. a diverse set of flavones, isosteric to 4(1h)-quinolones, were prepared and profiled for their antiplasmodial activity against the blood stage of p. falciparum w2 strain, and the liver stage of the rodent parasite plasmodium berghei. ligand efficient leads were identified as dual stage antimalarials, s ...201324125849
erythropoietin protects against murine cerebral malaria through actions on host cellular immunity.cerebral malaria (cm) is associated with excessive host proinflammatory responses and endothelial activation. the hematopoietic hormone erythropoietin (epo) possesses neuroprotective functions in animal models of ischemic-hypoxic, traumatic, and inflammatory injuries. in the plasmodium berghei anka model of experimental cm (ecm), recombinant human epo (rhepo) has shown evident protection against ecm. to elucidate the mechanism of epo in this ecm model, we investigated the effect of rhepo on host ...201424126529
cerebral tissue oxygenation impairment during experimental cerebral malaria.ischemia and hypoxia have been implicated in cerebral malaria (cm) pathogenesis, although direct measurements of hypoxia have not been conducted. c57bl/6 mice infected with plasmodium berghei anka (pba) develop a neurological syndrome known as experimental cerebral malaria (ecm), whereas balb/c mice are resistant to ecm. in this study, intravital microscopy methods were used to quantify hemodynamic changes, vascular/tissue oxygen (o₂) tension (po₂), and perivascular ph in vivo in ecm and non-ecm ...201324128424
3,5-bis(benzylidene)-4-piperidones and related n-acyl analogs: a novel cluster of antimalarials targeting the liver stage of plasmodium falciparum.drug resistance is a major challenge in antimalarial chemotherapy. in addition, a complete cure of malaria requires intervention at various stages in the development of the parasite within the host. there are only a few antimalarials that target the liver stage of the plasmodium species which is an essential part of the life cycle of the malarial parasite. we report a series of antimalarial 3,5-bis(benzylidene)-4-piperidones and related n-acyl analogs 1-5, a number of which exhibit potent in vit ...201324139941
effect of mature blood-stage plasmodium parasite sequestration on pathogen biomass in mathematical and in vivo models of malaria.parasite biomass and microvasculature obstruction are strongly associated with disease severity and death in plasmodium falciparum-infected humans. this is related to sequestration of mature, blood-stage parasites (schizonts) in peripheral tissue. the prevailing view is that schizont sequestration leads to an increase in pathogen biomass, yet direct experimental data to support this are lacking. here, we first studied parasite population dynamics in inbred wild-type (wt) mice infected with the r ...201424144725
ferrous iron-dependent drug delivery enables controlled and selective release of therapeutic agents in vivo.the precise targeting of cytotoxic agents to specific cell types or cellular compartments is of significant interest in medicine, with particular relevance for infectious diseases and cancer. here, we describe a method to exploit aberrant levels of mobile ferrous iron (fe(ii)) for selective drug delivery in vivo. this approach makes use of a 1,2,4-trioxolane moiety, which serves as an fe(ii)-sensitive "trigger," making drug release contingent on fe(ii)-promoted trioxolane fragmentation. we demon ...201324145449
evidence for pyronaridine as a highly effective partner drug for treatment of artemisinin-resistant malaria in a rodent model.the increasing prevalence in southeast asia of plasmodium falciparum infections with delayed parasite clearance rates, following treatment of malaria patients with the artemisinin derivative artesunate, highlights an urgent need to identify which of the currently available artemisinin-based combination therapies (acts) are most suitable to treat populations with emerging artemisinin resistance. here, we demonstrate that the rodent plasmodium berghei sana strain has acquired artemisinin resistanc ...201424145526
oxidative stress and micronutrient therapy in malaria: an in vivo study in plasmodium berghei infected mice.free radical production from oxidative stress induced by malaria infection plays a major role in the pathogenesis of malaria. however, the use of agents with antioxidant activity may interfere with malaria progression. the study involves an in vivo evaluation of the role of some antioxidant micronutrients in the modulation of malaria infection. rodent malaria model using plasmodium berghei nk-65 strain (chloroquine sensitive) was used for the study. forty five mice of either sex weighing 20.05 + ...201324171263
cytokine response to pregnancy-associated recrudescence of plasmodium berghei infection in mice with pre-existing immunity to malaria.during childhood, residents of areas with stable transmission of plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults therefore rarely experience clinical disease episodes. however, susceptibility to infection reappears in pregnant women, particularly primigravidae. this is due to appearance of antigenic parasite variants that are restricted to pregnancy. variant-specific immunity also governs pregnancy-associated recrudescence of plasmodium berghei infe ...201324180253
further evidence for an anti-inflammatory role of artesunate in experimental cerebral malaria.cerebral malaria (cm) is a clinical syndrome resulting from plasmodium falciparum infection. a wide range of clinical manifestations follow the disease including cognitive dysfunction, seizures and coma. cm pathogenesis remains incompletely understood and without treatment this condition is invariably fatal. artesunate has been accepted as the most effective drug for treating severe malaria. besides its antiparasitic activity, an anti-inflammatory property has also been reported. in the current ...201324180288
emerging roles for protein s-palmitoylation in toxoplasma biology.post-translational modifications are refined, rapidly responsive and powerful ways to modulate protein function. among post-translational modifications, acylation is now emerging as a widespread modification exploited by eukaryotes, bacteria and viruses to control biological processes. protein palmitoylation involves the attachment of palmitic acid, also known as hexadecanoic acid, to cysteine residues of integral and peripheral membrane proteins and increases their affinity for membranes. impor ...201424184909
functional roles for c5a and c5ar but not c5l2 in the pathogenesis of human and experimental cerebral malaria.the host immune response plays an important role in the onset and progression of cerebral malaria (cm). the complement system is an essential component of the innate immune response to malaria, and its activation generates the anaphylatoxin c5a. to test the hypothesis that c5a signaling contributes to the pathogenesis of cm, we investigated a causal role for the c5a receptors c5ar and c5l2 in a mouse model of experimental cm (ecm) induced by plasmodium berghei anka infection, and using a case-co ...201424191300
trem2 governs kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection.plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (trem2) and mhc class ii molecules as determinants of plasmodium berghei liver stage infection in mice. locus belr1 confers resistance to malaria liver stage infection. the use of newly derived subcongenic mouse lines allo ...201324218563
copper-transporting atpase is important for malaria parasite fertility.homeostasis of the trace element copper is essential to all eukaryotic life. copper serves as a cofactor in metalloenzymes and catalyses electron transfer reactions as well as the generation of potentially toxic reactive oxygen species. here, we describe the functional characterization of an evolutionarily highly conserved, predicted copper-transporting p-type atpase (cutp) in the murine malaria model parasite plasmodium berghei. live imaging of a parasite line expressing a fluorescently tagged ...201324237419
antimalarial efficacy of hydroxyethylapoquinine (sn-119) and its derivatives.quinine and other cinchona-derived alkaloids, although recently supplanted by the artemisinins (arts), continue to be important for treatment of severe malaria. quinine and quinidine have narrow therapeutic indices, and a safer quinine analog is desirable, particularly with the continued threat of antimalarial drug resistance. hydroxyethylapoquinine (heaq), used at 8 g a day for dosing in humans in the 1930s and halving mortality from bacterial pneumonias, was shown to cure bird malaria in the 1 ...201424247136
the effect of otostegia persica in combination with chloroquine on chloroquine-sensitive and chloroquine-resistant strains of plasmodium berghei using in-vivo fixed ratios method.malaria is one of the worldwide parasitic diseases which threaten the life of hundreds of millions of people at the malarious areas each year. the emergence of chloroquine-resistant strains of plasmodium falciparum in most of the malarious areas has encountered the relevant countries with some difficulties about treating the acute cases of the disease particulary if the monotherapy regimen has been used. because of many advantages for the combination therapy, the effectiveness of chloroquine (cq ...201224250482
in vitro and in vivo characterization of the antimalarial lead compound ssj-183 in plasmodium models.the objective of this work was to characterize the in vitro (plasmodium falciparum) and in vivo (plasmodium berghei) activity profile of the recently discovered lead compound ssj-183. the molecule showed in vitro a fast and strong inhibitory effect on growth of all p. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite str ...201324255594
plasmodium berghei calcium dependent protein kinase 1 is not required for host cell invasion.plasmodium calcium dependent protein kinase (cdpk1) is required for the development of sexual stages in the mosquito. in addition, it is proposed to play an essential role in the parasite's invasive stages possibly through the regulation of the actinomyosin motor and micronemal secretion. we demonstrate that plasmodium berghei cdpk1 is dispensable in the parasite's erythrocytic and pre-erythrocytic stages. we successfully disrupted p. berghei cdpk1 (pbcdpk1) by homologous recombination. the reco ...201324265753
in vivo antimalarial evaluation of mama decoction on plasmodium berghei in mice.the use of decoctions of different plant materials is common practice in antimalarial ethnomedicine in africa. scientific evaluation of such herbal combinations to verify the claims is important. the study has evaluated the antimalarial efficacy of mama decoction (md), a multicomponent herbal preparation and its individual plant components, namely leaves of morinda lucida benth [rubiaceae] (ml), azadirachta indica a. juss [meliaceae] (ai), alstonia boonei de wild [apocynaceae] (ab) and mangifera ...201424271081
a small molecule glycosaminoglycan mimetic blocks plasmodium invasion of the mosquito midgut.malaria transmission-blocking (t-b) interventions are essential for malaria elimination. small molecules that inhibit the plasmodium ookinete-to-oocyst transition in the midgut of anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. chondroitin sulfate glycosaminoglycans (cs-gags) on the anopheles gambiae midgut surface are putative ligands for plasmodium falciparum ookinetes. we hypothesized that our synthetic polysulfonated polymer, vs1, acting as a ...201324278017
defining the range of pathogens susceptible to ifitm3 restriction using a knockout mouse model.the interferon-inducible transmembrane (ifitm) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. further, single nucleotide polymorphisms (snps) in its sequence have been linked with risk of developing severe influenza virus infections in humans. the number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which ente ...201324278312
inhibitor of cysteine proteases is critical for motility and infectivity of plasmodium sporozoites.malaria is transmitted when motile sporozoites are injected into the dermis by an infected female anopheles mosquito. inside the mosquito vector, sporozoites egress from midgut-associated oocysts and eventually penetrate the acinar cells of salivary glands. parasite-encoded factors with exclusive vital roles in the insect vector can be studied by classical reverse genetics. here, we characterized the in vivo roles of plasmodium berghei falstatin/icp (inhibitor of cysteine proteases). this protei ...201324281719
malaria infection alters the expression of hepatobiliary and placental drug transporters in pregnant mice.preventing and treating malaria in pregnancy is a global health priority. however little is known regarding the impact of malaria infection on the maternal and fetal disposition of pharmaceuticals and other xenobiotics. our objective was to characterize expression of key determinants of drug-disposition in maternal and fetal tissues in a validated murine model of experimental placental malaria. balb/c mice were infected with plasmodium berghei at mid gestation [gestational day (gd) 13] and mater ...201424281836
cost of immune priming within generations: trade-off between infection and reproduction.immune priming is a new paradigm in innate immunity. however, most studies have focused on the benefits of priming (enhanced survival and parasite clearance after a second challenge), while little attention has been paid to the costs. in this study, both factors were investigated in anopheles albimanus primed against plasmodium berghei. as previously observed in other invertebrates, compared to un-primed mosquitoes, those primed better controlled a challenge from the same parasite, and had a hig ...201424291714
hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro.homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. in vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possib ...201324291761
in vitro antiplasmodial activity, cytotoxicity and chemical profiles of sponge species of cuban coasts.aqueous and organic fractions from the crude extracts of 17 sponge species collected at boca de calderas, havana, cuba were analysed. the organic fractions of mycale laxissima, clathria echinata and agelas cerebrum exhibited values of concentrations causing 50% inhibition of in vitro growth of plasmodium berghei (ic50) of 42.3 ± 5.1, 52 ± 9.7 and 60.3 ± 10.6 μg/ml, respectively, while their selectivity indexes for fibroblast cell lines were 9.45, 4.24 and 8.7, correspondingly. these fractions re ...201424304347
endogenous mouse mammary tumor viruses (mtv): new roles for an old virus in cancer, infection, and immunity.mouse mammary tumor viruses are beta-retroviruses that exist in both exogenous (mmtv) and endogenous (mtv) forms. exogenous mmtv is transmitted via the milk of lactating animals and is capable of inducing mammary gland tumors later in life. mmtv has provided a number of critical models for studying both viral infection as well as human breast cancer. in addition to the horizontally transmitted mmtv, most inbred mouse strains contain permanently integrated mtv proviruses within their genome that ...201324324930
characterization of the atg8-conjugation system in 2 plasmodium species with special focus on the liver stage: possible linkage between the apicoplastic and autophagic systems?plasmodium parasites successfully colonize different habitats within mammals and mosquitoes, and adaptation to various environments is accompanied by changes in their organelle composition and size. previously, we observed that during hepatocyte infection, plasmodium discards organelles involved in invasion and expands those implicated in biosynthetic pathways. we hypothesized that this process is regulated by autophagy. plasmodium spp. possess a rudimentary set of known autophagy-related protei ...201424342964
the malarial serine protease sub1 plays an essential role in parasite liver stage development.transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. the resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. these are released to initiate the blood stage life cycle, which causes all the pathology associated with the disease. whilst elements of liver stage merozoite biology are similar to those in the much bette ...201324348254
stress granules and plasmodium liver stage infection.organisms have evolved numerous strategies to control infection by an array of intracellular pathogens. one cell autonomous pathogen control strategy is global inhibition of protein synthesis via stress granule (sg) formation. sgs are induced by stressful stimuli such as oxidative stress and nutrient deprivation, and are known to counteract both viral and bacterial infections. pathogens, in turn, may actively block an infected cell's ability to form sgs. in vitro and in vivo, many liver stage ma ...201424357231
alpha-tocopherol transfer protein gene inhibition enhances the acquired immune response during malaria infection in mice.immune response to malaria infection is complex and seems to be regulated by innate and adaptive immune response as well as environmental factors such as host genetics and nutritional status. previously, we have reported that α-tocopherol transfer protein knockout (α-ttp(δ)) mice, showing low concentrations of α-tocopherol in circulation, infected with plasmodium berghei nk65 survived significantly longer as compared with the wild-type mice. in addition, plasmodium yoelii xl-17, a lethal strain, ...201424363183
dihydroquinazolinone inhibitors of proliferation of blood and liver stage malaria parasites.drugs that target both the liver and blood stages of malaria will be needed to reduce the disease's substantial worldwide morbidity and mortality. evaluation of a 259-member library of compounds that block proliferation of the blood stage of malaria revealed several scaffolds--dihydroquinazolinones, phenyldiazenylpyridines, piperazinyl methyl quinolones, and bis-benzimidazoles--with promising activity against the liver stage. focused structure-activity studies on the dihydroquinazolinone scaffol ...201324366746
plasmodium berghei sporozoites acquire virulence and immunogenicity during mosquito hemocoel transit.malaria is a vector-borne disease caused by the single-cell eukaryote plasmodium. the infectious parasite forms are sporozoites, which originate from midgut-associated oocysts, where they eventually egress and reach the mosquito hemocoel. sporozoites actively colonize the salivary glands in order to be transmitted to the mammalian host. whether residence in the salivary glands provides distinct and vital cues for the development of infectivity remains unsolved. in this study, we systematically c ...201324379288
interleukin-3-deficient mice have increased resistance to blood-stage malaria.the contribution of interleukin-3 (il-3), a hematopoietic growth factor and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting il-3-deficient (knockout [ko]) mice with plasmodium berghei nk65. male il-3 ko mice, but not female mice, were more resistant to infection than wild-type (wt) mice, as evidenced by lower peak parasitemia and prolonged survival. both male and female il-3 ko mice had increased splenomegaly and were more anemic than corresponding w ...201424379292
efficacy of a plasmodium vivax malaria vaccine using chad63 and modified vaccinia ankara expressing thrombospondin-related anonymous protein as assessed with transgenic plasmodium berghei parasites.plasmodium vivax is the world's most widely distributed malaria parasite and a potential cause of morbidity and mortality for approximately 2.85 billion people living mainly in southeast asia and latin america. despite this dramatic burden, very few vaccines have been assessed in humans. the clinically relevant vectors modified vaccinia virus ankara (mva) and the chimpanzee adenovirus chad63 are promising delivery systems for malaria vaccines due to their safety profiles and proven ability to in ...201324379295
tafenoquine and npc-1161b require cyp 2d metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds.tafenoquine (tq) is an 8-aminoquinoline (8aq) that has been tested in several phase ii and phase iii clinical studies and is currently in late stage development as an anti-malarial prophylactic agent. npc-1161b is a promising 8aq in late preclinical development. it has recently been reported that the 8aq drug primaquine requires metabolic activation by cyp 2d6 for efficacy in humans and in mice, highlighting the importance of pharmacogenomics in the target population when administering primaquin ...201424386891
toxoplasma gondii upregulates interleukin-12 to prevent plasmodium berghei-induced experimental cerebral malaria.a chronic infection with the parasite toxoplasma gondii has previously been shown to protect mice against subsequent viral, bacterial, or protozoal infections. here we have shown that a chronic t. gondii infection can prevent plasmodium berghei anka-induced experimental cerebral malaria (ecm) in c57bl/6 mice. treatment with soluble t. gondii antigens (stag) reduced parasite sequestration and t cell infiltration in the brains of p. berghei-infected mice. administration of stag also preserved bloo ...201424396042
flt3 ligand treatment modulates parasitemia during infection with rodent malaria parasites via myd88- and ifn-γ-dependent mechanisms.we previously showed that treatment of mice with the flt3 ligand (flt3l) prevents development of lethal experimental cerebral malaria and inhibits parasitemia during plasmodium berghei anka (pba) infection. in this study, we investigated the mechanisms underlying the reduction of parasitemia in flt3l-treated mice. studies using gene knockout mice and antibody treatment indicated that the anti-parasitemia effect of flt3l was mediated by innate immune system and was dependent on myd88, ifn-γ, il-1 ...201424400637
simple, sensitive and quantitative bioluminescence assay for determination of malaria pre-patent period.the first phase of malaria infection occurs in the liver and is clinically silent. inside hepatocytes each plasmodium sporozoite replicate into thousands of erythrocyte-infectious merozoites that when released into the blood stream result in clinical symptoms of the disease. the time between sporozoite inoculation and the appearance of parasites in the blood is defined as the pre-patent period, which is classically analysed by time-consuming and labor-intensive techniques, such as microscopy and ...201424400642
the role of pro-resolution lipid mediators in infectious disease.inflammation is an essential host defence against infection, but can be damaging when excessive. resolution of inflammation is an active process, and the pro-resolution effects of lipoxins, resolvins and protectins have received significant interest. here, we review emerging data on the role of these lipid mediators in infectious disease. lipoxins influence host control of mycobacterium tuberculosis, toxoplasma gondii, trypanosoma cruzi and plasmodium berghei cerebral malaria in mice. their effe ...201424400794
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