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a genetic study of the susceptibility of anopheles gambiae to plasmodium berghei.in a study of the genetics of susceptibility and refractoriness of anopheles gambiae to plasmodium species, nine generations of selection resulted in a completely susceptible line and an entirely refractory line to plasmodium berghei (a rodent malaria). the f1 progeny from reciprocal crosses between the lines differed in their susceptibility to the parasite. backcrosses to the parent did not produce proportions of susceptible and refractory individuals consistent with single gene inheritance or ...19807010688
mapping a quantitative trait locus involved in melanotic encapsulation of foreign bodies in the malaria vector, anopheles gambiae.a plasmodium-refractory strain of anopheles gambiae melanotically encapsulates many species of plasmodium, whereas wild-type mosquitoes are usually susceptible. this encapsulation trait can also be observed by studying the response of refractory and susceptible strains to intrathoracically injected cm-sephadex beads. we report the results of broad-scale quantitative trait locus (qtl) mapping of the encapsulation trait using the bead model system. interval mapping using the method of maximum like ...19979215900
plasmodium activates the innate immune response of anopheles gambiae mosquitoes.innate immune-related gene expression in the major disease vector mosquito anopheles gambiae has been analyzed following infection by the malaria parasite, plasmodium berghei. substantially increased levels of mrnas encoding the antibacterial peptide defensin and a putative gram-negative bacteria-binding protein (gnbp) are observed 20-30 h after ingestion of an infected blood-meal, at a time which indicates that this induction is a response to parasite invasion of the midgut epithelium. the indu ...19979321391
malaria infection of the mosquito anopheles gambiae activates immune-responsive genes during critical transition stages of the parasite life cycle.six gene markers have been used to map the progress of the innate immune response of the mosquito vector, anopheles gambiae, upon infection by the malaria parasite, plasmodium berghei. in addition to four previously reported genes, the set of markers included nos (a nitric oxide synthase gene fragment) and ichit (a gene encoding two putative chitin-binding domains separated by a polythreonine-rich mucin region). in the midgut, a robust response occurs at 24 h post-infection, at a time when malar ...19989799221
plasmodium berghei: induction of aminopeptidase in malaria-resistant strain of anopheles gambiae. 199910502473
molecular characterization of five serine protease genes cloned from anopheles gambiae hemolymph.we identified five new serine protease cdnas from the hemolymph of the malaria vector, anopheles gambiae. all five show sequence similarity to genes thought to be involved in vertebrate or invertebrate defense responses. sp14a, sp14d2 and sp22d demonstrate changes in transcript abundance in response to bacteria injections. sp14a and sp14d2, as well as the previously characterized sp14d1, are induced by infection with the malaria parasite, plasmodium berghei. these three proteases, along with sp1 ...200010646969
anopheles gambiae laminin interacts with the p25 surface protein of plasmodium berghei ookinetes.laminin is a major constituent of the basal lamina surrounding the midgut of the malaria vectors that has been implicated in the development of the plasmodium oocyst. in this report we describe the cloning of the anopheles gambiae gene encoding the laminin gamma 1 polypeptide and follow its expression during mosquito development. to further investigate the putative role of laminin in the transmission of the malaria parasite we studied the potential binding of the p25 surface protein of plasmodiu ...200111223130
design and activity of antimicrobial peptides against sporogonic-stage parasites causing murine malarias.insects produce several types of peptides to combat a broad spectrum of invasive pathogenic microbes, including protozoans. however, despite this defense response, infections are often established. our aim was to design novel peptides that produce high rates of mortality among protozoa of the genus plasmodium, the malaria parasites. using existing antimicrobial peptide sequences as templates, we designed and synthesized three short novel hybrids, designated vida1 to vida3. each has a slightly di ...200212069961
reverse genetics in the mosquito anopheles gambiae: targeted disruption of the defensin gene.anopheles gambiae, the major vector of human malaria parasite, is an important insect model to study vector-parasite interactions. here, we developed a simple in vivo double-stranded rna (dsrna) knockout approach to determine the function of the mosquito antimicrobial peptide gene defensin. we injected dsrna into adults and observed efficient and reproducible silencing of defensin. analysis of the knockdown phenotype revealed that this peptide is required for the mosquito antimicrobial defense a ...200212189180
cloning and characterization of four anopheles gambiae serpin isoforms, differentially induced in the midgut by plasmodium berghei invasion.the genomic locus srpn10 of the malaria vector anopheles gambiae codes for four alternatively spliced serine protease inhibitors of the serpin superfamily. the four 40- to 42-kda isoforms differ only at their c terminus, which bears the reactive site loop, and exhibit protein sequence similarity with other insect serpins and mammalian serpins of the ovalbumin family. inhibition experiments with recombinant purified srpn10 serpins reveal distinct and specific inhibitory activity of three isoforms ...200312456678
immune response of anopheles gambiae to the early sporogonic stages of the human malaria parasite plasmodium falciparum.deciphering molecular interactions between the malaria parasite and its mosquito vector is an emerging area of research that will be greatly facilitated by the recent sequencing of the genomes of anopheles gambiae mosquito and of various plasmodium species. so far, most such studies have focused on plasmodium berghei, a parasite species that infects rodents and is more amenable to studies. here, we analysed the expression pattern of nine an.gambiae genes involved in immune surveillance during de ...200212485988
the dynamics of interactions between plasmodium and the mosquito: a study of the infectivity of plasmodium berghei and plasmodium gallinaceum, and their transmission by anopheles stephensi, anopheles gambiae and aedes aegypti.knowledge of parasite-mosquito interactions is essential to develop strategies that will reduce malaria transmission through the mosquito vector. in this study we investigated the development of two model malaria parasites, plasmodium berghei and plasmodium gallinaceum, in three mosquito species anopheles stephensi, anopheles gambiae and aedes aegypti. new methods to study gamete production in vivo in combination with gfp-expressing ookinetes were employed to measure the large losses incurred by ...200312906877
complement-like protein tep1 is a determinant of vectorial capacity in the malaria vector anopheles gambiae.anopheles mosquitoes are major vectors of human malaria in africa. large variation exists in the ability of mosquitoes to serve as vectors and to transmit malaria parasites, but the molecular mechanisms that determine vectorial capacity remain poorly understood. we report that the hemocyte-specific complement-like protein tep1 from the mosquito anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite plasmodium berghei. the dsrna knockdown of tep1 in adults ...200415006349
ectopic expression of a cecropin transgene in the human malaria vector mosquito anopheles gambiae (diptera: culicidae): effects on susceptibility to plasmodium.genetically altering the disease vector status of insects using recombinant dna technologies is being considered as an alternative to eradication efforts. manipulating the endogenous immune response of mosquitoes such as the temporal and special expression of antimicrobial peptides like cecropin may result in a refractory phenotype. using transgenic technology a unique pattern of expression of cecropin a (ceca) in anopheles gambiae was created such that ceca was expressed beginning 24 h after a ...200415185949
overexpression and altered nucleocytoplasmic distribution of anopheles ovalbumin-like srpn10 serpins in plasmodium-infected midgut cells.the design of effective, vector-based malaria transmission blocking strategies relies on a thorough understanding of the molecular and cellular interactions that occur during the parasite sporogonic cycle in the mosquito. during plasmodium berghei invasion, transcription from the srpn10 locus, encoding four serine protease inhibitors of the ovalbumin family, is strongly induced in the mosquito midgut. herein we demonstrate that intense induction as well as redistribution of srpn10 occurs specifi ...200515659062
the anopheles gambiae gamma1 laminin directly binds the plasmodium berghei circumsporozoite- and trap-related protein (ctrp). 200515694493
immune signaling pathways regulating bacterial and malaria parasite infection of the mosquito anopheles gambiae.we show that, in the malaria vector anopheles gambiae, expression of cecropin 1 is regulated by rel2, an nf-kappab-like transcription factor orthologous to drosophila relish. through alternative splicing, rel2 produces a full-length (rel2-f) and a shorter (rel2-s) protein isoform lacking the inhibitory ankyrin repeats and death domain. rna interference experiments show that, in contrast to drosophila relish, which responds solely to gram-negative bacteria, the anopheles rel2-f and rel2-s isoform ...200516076953
malaria parasites in mosquitoes: laboratory models, evolutionary temptation and the real world.a recent study describing the effect of plasmodium berghei infection on some anopheles gambiae immune genes demonstrates that p. berghei is responsible for the upregulation of several genes involved in the immune response that affect parasitic development differently during the ookinete-to-oocyst developmental transition. it is important to question the relevance of such results, which are based on a laboratory model system, when discussing host-parasite interactions and, especially, the develop ...200516099724
effect of chloroquine on the expression of genes involved in the mosquito immune response to plasmodium infection.chloroquine has been described to increase plasmodium infectivity to the mosquito vector and is known to affect the vertebrate host immune response including during malarial infection. although knowledge of the mosquito immune response has recently improved, nothing is known about the impact of chloroquine on mosquito immunity. in order to characterize the influence of chloroquine on the mosquito immune system, we have analyzed the effect of chloroquine on anopheles gambiae (i) serine proteases ...200516102418
anopheles gambiae srpn2 facilitates midgut invasion by the malaria parasite plasmodium berghei.we report on a phylogenetic and functional analysis of genes encoding three mosquito serpins (srpn1, srpn2 and srpn3), which resemble known inhibitors of prophenoloxidase-activating enzymes in other insects. following rna interference induction by double-stranded rna injection, knockdown of srpn2 in adult anopheles gambiae produced a notable phenotype: the appearance of melanotic pseudotumours, which increased in size and number with time, indicating spontaneous melanization and association with ...200516113656
close association of invading plasmodium berghei and beta integrin in the anopheles gambiae midgut.we have used confocal microscopy and an antibody against anopheles gambiae beta integrin to study this protein's distribution in the mosquito midgut and its relationship to invading plasmodium berghei parasites. an extensive reorganization of integrin is seen to take place in the midgut epithelial cells following the uptake of either non-infected or parasite-infected blood meal, probably reflecting the reshaping of the gut due to the presence of the food bolus and the peritrophic membrane that s ...200516116619
bypassing the midgut results in development of plasmodium berghei oocysts in a refractory strain of anopheles gambiae (diptera: culicidae).the l35 strain of anopheles gambiae giles was genetically selected for its ability to melanize and kill malaria parasites. a wide range of plasmodium species are subject to this response when orally ingested, including the rodent malaria, p. berghei. however, when we directly injected p. berghei into the hemocoel, we found that parasites developed normally to the oocyst stage. this work suggests that the parasite melanization response depends on the interaction of the ookinetes and the midgut. t ...200516119566
using green fluorescent malaria parasites to screen for permissive vector mosquitoes.the plasmodium species that infect rodents, particularly plasmodium berghei and plasmodium yoelii, are useful to investigate host-parasite interactions. the mosquito species that act as vectors of human plasmodia in south east asia, africa and south america show different susceptibilities to infection by rodent plasmodium species. p. berghei and p. yoelii infect both anopheles gambiae and anopheles stephensi, which are found mainly in africa and asia, respectively. however, it was reported that ...200616569221
differential gene expression in abdomens of the malaria vector mosquito, anopheles gambiae, after sugar feeding, blood feeding and plasmodium berghei infection.large scale sequencing of cdna libraries can provide profiles of genes expressed in an organism under defined biological and environmental circumstances. we have analyzed sequences of 4541 expressed sequence tags (ests) from 3 different cdna libraries created from abdomens from plasmodium infection-susceptible adult female anopheles gambiae. these libraries were made from sugar fed (s), rat blood fed (rb), and p. berghei-infected (irb) mosquitoes at 30 hours after the blood meal, when most paras ...200616712725
anopheles and plasmodium: from laboratory models to natural systems in the field.parasites that cause malaria must complete a complex life cycle in anopheles vector mosquitoes in order to be transmitted from human to human. previous gene-silencing studies have shown the influence of mosquito immunity in controlling the development of plasmodium. thus, parasite survival to the oocyst stage increased when the parasite antagonist gene lrim1 (leucine-rich repeat immune protein 1) of the mosquito was silenced, but decreased when the c-type lectin agonist gene ctl4 or ctlma2 (ctl ...200617099691
fz2 and cdc42 mediate melanization and actin polymerization but are dispensable for plasmodium killing in the mosquito midgut.the midgut epithelium of the mosquito malaria vector anopheles is a hostile environment for plasmodium, with most parasites succumbing to host defenses. this study addresses morphological and ultrastructural features associated with plasmodium berghei ookinete invasion in anopheles gambiae midguts to define the sites and possible mechanisms of parasite killing. we show by transmission electron microscopy and immunofluorescence that the majority of ookinetes are killed in the extracellular space. ...200617196037
efficiency of salivary gland invasion by malaria sporozoites is controlled by rapid sporozoite destruction in the mosquito haemocoel.for successful transmission to the vertebrate host, malaria sporozoites must migrate from the mosquito midgut to the salivary glands. here, using purified sporozoites inoculated into the mosquito haemocoel, we show that salivary gland invasion is inefficient and that sporozoites have a narrow window of opportunity for salivary gland invasion. only 19% of sporozoites invade the salivary glands, all invasion occurs within 8h at a rate of approximately 200 sporozoites per hour, and sporozoites that ...200717275826
carboxypeptidases b of anopheles gambiae as targets for a plasmodium falciparum transmission-blocking vaccine.anopheles gambiae is the major african vector of plasmodium falciparum, the most deadly species of human malaria parasite and the most prevalent in africa. several strategies are being developed to limit the global impact of malaria via reducing transmission rates, among which are transmission-blocking vaccines (tbvs), which induce in the vertebrate host the production of antibodies that inhibit parasite development in the mosquito midgut. so far, the most promising components of a tbv are paras ...200717283100
malaria plasmodium agent induces alteration in the head proteome of their anopheles mosquito host.despite increasing evidence of behavioural manipulation of their vectors by pathogens, the underlying mechanisms causing infected vectors to act in ways that benefit pathogen transmission remain enigmatic in most cases. here, 2-d dige coupled with ms were employed to analyse and compare the head proteome of mosquitoes (anopheles gambiae sensu stricto (giles)) infected with the malarial parasite (plasmodium berghei) with that of uninfected mosquitoes. this approach detected altered levels of 12 p ...200717464940
structural basis for conserved complement factor-like function in the antimalarial protein tep1.thioester-containing proteins (teps) are a major component of the innate immune response of insects to invasion by bacteria and protozoa. teps form a distinct clade of a superfamily that includes the pan-protease inhibitors alpha(2)-macroglobulins and vertebrate complement factors. the essential feature of these proteins is a sequestered thioester bond that, after cleavage in a protease-sensitive region of the protein, is activated and covalently binds to its target. recently, tep1 from the mala ...200717606907
disruption of plasmodium falciparum development by antibodies against a conserved mosquito midgut antigen.malaria parasites must undergo development within mosquitoes to be transmitted to a new host. antivector transmission-blocking vaccines inhibit parasite development by preventing ookinete interaction with mosquito midgut ligands. therefore, the discovery of novel midgut antigen targets is paramount. jacalin (a lectin) inhibits ookinete attachment by masking glycan ligands on midgut epithelial surface glycoproteins. however, the identities of these midgut glycoproteins have remained unknown. here ...200717673553
the salivary glands and saliva of anopheles gambiae as an essential step in the plasmodium life cycle: a global proteomic study.proteins synthesized in the salivary glands of the anopheles gambiae mosquito are thought to be important in the life cycle of the malaria parasite plasmodium. to describe a. gambiae salivary gland and saliva contents, we combined several techniques: 1-de, 2-de and lc ms/ms. this study has identified five saliva proteins and 122 more proteins from the salivary glands, including the first proteomic description for 89 of these salivary gland proteins. since the invasion and sporozoite maturation t ...200717849406
continuous exposure to plasmodium results in decreased susceptibility and transcriptomic divergence of the anopheles gambiae immune system.plasmodium infection has been shown to compromise the fitness of the mosquito vector, reducing its fecundity and longevity. however, from an evolutionary perspective, the impact of plasmodium infection as a selective pressure on the mosquito is largely unknown.200718053261
reactive oxygen species modulate anopheles gambiae immunity against bacteria and plasmodium.the involvement of reactive oxygen species (ros) in mosquito immunity against bacteria and plasmodium was investigated in the malaria vector anopheles gambiae. strains of an. gambiae with higher systemic levels of ros survive a bacterial challenge better, whereas reduction of ros by dietary administration of antioxidants significantly decreases survival, indicating that ros are required to mount effective antibacterial responses. expression of several ros detoxification enzymes increases in the ...200818065421
serial analysis of gene expression in plasmodium berghei salivary gland sporozoites.the invasion of anopheles salivary glands by plasmodium sporozoites is an essential step for transmission of the parasite to the vertebrate host. salivary gland sporozoites undergo a developmental programme to express genes required for their journey from the site of the mosquito bite to the liver and subsequent invasion of, and development within, hepatocytes. a serial analysis of gene expression was performed on anopheles gambiae salivary glands infected or not with plasmodium berghei and we r ...200718093287
the gram-negative bacteria-binding protein gene family: its role in the innate immune system of anopheles gambiae and in anti-plasmodium defence.gram-negative bacteria-binding proteins (gnbps) are pattern recognition receptors which contribute to the defensive response against plasmodium infection in anopheles. we have characterized the gnbp gene family in anopheles gambiae at the molecular level, and show that they are functionally diverse components of the a. gambiae innate immune system. gnbpb4 is a major factor in the defence against a broad range of pathogens, while the other gnbps have narrower defence specificities. gnbpb4 is asso ...200818237283
the microneme proteins ctrp and soap are not essential for plasmodium berghei ookinete to oocyst transformation in vitro in a cell free system.two plasmodium berghei ookinete micronemal proteins, circumsporozoite and trap related protein (ctrp) and secreted ookinete adhesive protein (soap) both interact with the basal lamina component laminin. following gene disruption studies it has been proposed that, apart from their role in motility, these proteins may be required for interactions leading to ookinete-to-oocyst transformation.200818489758
transmission blocking immunity in the malaria non-vector mosquito anopheles quadriannulatus species a.despite being phylogenetically very close to anopheles gambiae, the major mosquito vector of human malaria in africa, anopheles quadriannulatus is thought to be a non-vector. understanding the difference between vector and non-vector mosquitoes can facilitate development of novel malaria control strategies. we demonstrate that an. quadriannulatus is largely resistant to infections by the human parasite plasmodium falciparum, as well as by the rodent parasite plasmodium berghei. by using genetics ...200818497855
use of a drosophila model to identify genes regulating plasmodium growth in the mosquito.we performed a forward genetic screen, using drosophila as a surrogate mosquito, to identify host factors required for the growth of the avian malaria parasite, plasmodium gallinaceum. we identified 18 presumed loss-of-function mutants that reduced the growth of the parasite in flies. presumptive mutation sites were identified in 14 of the mutants on the basis of the insertion site of a transposable element. none of the identified genes have been previously implicated in innate immune responses ...200818791251
anopheles gambiae apl1 is a family of variable lrr proteins required for rel1-mediated protection from the malaria parasite, plasmodium berghei.we previously identified by genetic mapping an anopheles gambiae chromosome region with strong influence over the outcome of malaria parasite infection in nature. candidate gene studies in the genetic interval, including functional tests using the rodent malaria parasite plasmodium berghei, identified a novel leucine-rich repeat gene, apl1, with functional activity against p. berghei.200818989366
leucine-rich repeat protein complex activates mosquito complement in defense against plasmodium parasites.leucine-rich repeat-containing proteins are central to host defense in plants and animals. we show that in the mosquito anopheles gambiae, two such proteins that antagonize malaria parasite infections, lrim1 and apl1c, circulate in the hemolymph as a high-molecular-weight complex held together by disulfide bridges. the complex interacts with the complement c3-like protein, tep1, promoting its cleavage or stabilization and its subsequent localization on the surface of midgut-invading plasmodium b ...200919264986
a possible mechanism for the suppression of plasmodium berghei development in the mosquito anopheles gambiae by the microsporidian vavraia culicis.microsporidian parasites of mosquitoes offer a possible way of controlling malaria, as they impede the development of plasmodium parasites within the mosquito. the mechanism involved in this interference process is unknown.200919277119
caspar controls resistance to plasmodium falciparum in diverse anopheline species.immune responses mounted by the malaria vector anopheles gambiae are largely regulated by the toll and imd (immune deficiency) pathways via the nf-kappab transcription factors rel1 and rel2, which are controlled by the negative regulators cactus and caspar, respectively. rel1- and rel2-dependent transcription in a. gambiae has been shown to be particularly critical to the mosquito's ability to manage infection with the rodent malaria parasite plasmodium berghei. using rna interference to deplete ...200919282971
plasmodium chabaudi: expression of active recombinant chabaupain-1 and localization studies in anopheles sp.plasmodium cysteine proteases have been shown to be immunogenic and are being used as malaria potential serodiagnostic markers and vaccine targets. genes encoding two plasmodium chabaudi cysteine proteases chabaupain-1 (cp-1) and chabaupain-2 (cp-2) were identified and further expressed in escherichia coli. solubilisation of recombinant cp-1 and cp-2 was achieved by decreasing the temperature of induction. anopheles gambiae tissues infected with plasmodium were analyzed by western blotting using ...200919292986
anopheles gambiae croquemort scrbq2, expression profile in the mosquito and its potential interaction with the malaria parasite plasmodium berghei.the scavenger receptor family comprises transmembrane proteins involved in the recognition of polyanionic ligands. several studies have established that members of this family are involved both in immunity and in developmental processes. in drosophila melanogaster, one of the best characterized scavenger receptors is croquemort, which participates in the recognition of apoptotic cells in the embryo. although comparative genomic studies have revealed the presence of four orthologs of this recepto ...200919366631
genome-wide transcriptomic profiling of anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and plasmodium berghei infection.the mosquito anopheles gambiae is a major vector of human malaria. increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. to further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female an. gambiae hemocytes following infection by two species of bacteria and a malaria parasite.200919500340
anopheles gambiae pgrplc-mediated defense against bacteria modulates infections with malaria parasites.recognition of peptidoglycan (pgn) is paramount for insect antibacterial defenses. in the fruit fly drosophila melanogaster, the transmembrane pgn recognition protein lc (pgrp-lc) is a receptor of the imd signaling pathway that is activated after infection with bacteria, mainly gram-negative (gram-). here we demonstrate that bacterial infections of the malaria mosquito anopheles gambiae are sensed by the orthologous pgrplc protein which then activates a signaling pathway that involves the rel/nf ...200919662170
discovery of plasmodium modulators by genome-wide analysis of circulating hemocytes in anopheles gambiae.insect hemocytes mediate important cellular immune responses including phagocytosis and encapsulation and also secrete immune factors such as opsonins, melanization factors, and antimicrobial peptides. however, the molecular composition of these important immune cells has not been elucidated in depth, because of their scarcity in the circulating hemolymph, their adhesion to multiple tissues and the lack of primary culture methods to produce sufficient material for a genome-wide analysis. in this ...200919940242
mosquito cell line glycoproteins: an unsuitable model system for the plasmodium ookinete-mosquito midgut interaction?abstract:201020338056
anopheles gambiae prs1 modulates plasmodium development at both midgut and salivary gland steps.invasion of the mosquito salivary glands by plasmodium is a critical step for malaria transmission. from a sage analysis, we previously identified several genes whose expression in salivary glands was regulated coincident with sporozoite invasion of salivary glands. to get insights into the consequences of these salivary gland responses, here we have studied one of the genes, prs1 (plasmodium responsive salivary 1), whose expression was upregulated in infected glands, using immunolocalization an ...201020634948
apolipophorin-iii mediates antiplasmodial epithelial responses in anopheles gambiae (g3) mosquitoes.apolipophorin-iii (apolp-iii) is known to play an important role in lipid transport and innate immunity in lepidopteran insects. however, there is no evidence of involvement of apolp-iiis in the immune responses of dipteran insects such as drosophila and mosquitoes.201021072214
energy metabolism affects susceptibility of anopheles gambiae mosquitoes to plasmodium infection.previous studies showed that anopheles gambiae l3-5 females, which are refractory (r) to plasmodium infection, express higher levels of genes involved in redox-metabolism and mitochondrial respiration than susceptible (s) g3 females. our studies revealed that r females have reduced longevity, faster utilization of lipid reserves, impaired mitochondrial state-3 respiration, increased rate of mitochondrial electron leak and higher expression levels of several glycolytic enzyme genes. furthermore, ...201121320598
infection intensity dependent responses of anopheles gambiae to african malaria parasites plasmodium falciparum.malaria remains a devastating disease despite efforts for control and prevention. extensive studies using mostly rodent infection models reveal that successful plasmodium parasite transmission by the african mosquito vector anopheles gambiae depends on finely tuned vector/parasite interactions. here we investigate the transcriptional response of a. gambiae to geographically related plasmodium falciparum populations at varying infection intensities and different infection stages. these responses ...201121844236
The interplay between tubulins and P450 cytochromes during Plasmodium berghei invasion of Anopheles gambiae midgut.Plasmodium infection increases the oxidative stress inside the mosquito, leading to a significant alteration on transcription of Anopheles gambiae detoxification genes. Among these detoxification genes several P450 cytochromes and tubulins were differently expressed, suggesting their involvement in the mosquito's response to parasite invasion. P450 cytochromes are usually involved in the metabolism and detoxification of several compounds, but are also regulated by several pathogens, including ma ...201121912622
wolbachia strain walbb enhances infection by the rodent malaria parasite plasmodium berghei in anopheles gambiae mosquitoes.wolbachia, a common bacterial endosymbiont of insects, has been shown to protect its hosts against a wide range of pathogens. however, not all strains exert a protective phenotype on their host. here we assess the affect of two divergent wolbachia strains, walbb from aedes albopticus and wmelpop from drosophila melanogaster, on the vector competence of anopheles gambiae challenged with plasmodium berghei. we show the walbb strain significantly increases p. berghei oocyst levels in the mosquito m ...201122210220
visualizing non infectious and infectious anopheles gambiae blood feedings in naive and saliva-immunized mice.anopheles gambiae is a major vector of malaria and lymphatic filariasis. the arthropod-host interactions occurring at the skin interface are complex and dynamic. we used a global approach to describe the interaction between the mosquito (infected or uninfected) and the skin of mammals during blood feeding.201223272060
mosquito akirin as a potential antigen for malaria control.the control of vector-borne diseases is important to improve human and animal health worldwide. malaria is one of the world's deadliest diseases and is caused by protozoan parasites of the genus plasmodium, which are transmitted by anopheles spp. mosquitoes. recent evidences using subolesin (sub) and akirin (akr) vaccines showed a reduction in the survival and/or fertility of blood-sucking ectoparasite vectors and the infection with vector-borne pathogens. these experiments suggested the possibi ...201425472895
functional genomic analyses of enterobacter, anopheles and plasmodium reciprocal interactions that impact vector competence.malaria exerts a tremendous socioeconomic impact worldwide despite current control efforts, and novel disease transmission-blocking strategies are urgently needed. the enterobacter bacterium esp_z, which is naturally harboured in the mosquito midgut, can inhibit the development of plasmodium parasites prior to their invasion of the midgut epithelium through a mechanism that involves oxidative stress. here, a multifaceted approach is used to study the tripartite interactions between the mosquito, ...201627549662
anopheles gambiae antiviral immune response to systemic o'nyong-nyong infection.mosquito-borne viral diseases cause significant burden in much of the developing world. although host-virus interactions have been studied extensively in the vertebrate host, little is known about mosquito responses to viral infection. in contrast to mosquitoes of the aedes and culex genera, anopheles gambiae, the principal vector of human malaria, naturally transmits very few arboviruses, the most important of which is o'nyong-nyong virus (onnv). here we have investigated the a. gambiae immune ...201222428080
phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.the blood meal of the female malaria mosquito is a pre-requisite to egg production and also represents the transmission route for the malaria parasite. the proper and rapid assimilation of proteins and nutrients in the blood meal creates a significant metabolic challenge for the mosquito. to better understand this process we generated a global profile of metabolite changes in response to blood meal of anopheles gambiae, using gas chromatography-mass spectrometry (gc-ms). to disrupt a key pathway ...201424409310
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
resisting infection by plasmodium berghei increases the sensitivity of the malaria vector anopheles gambiae to ddt.the evolution of insecticide resistance threatens current malaria control methods, which rely heavily on chemical insecticides. the magnitude of the threat will be determined by the phenotypic expression of resistance in those mosquitoes that can transmit malaria. these differ from the majority of the mosquito population in two main ways; they carry sporozoites (the infectious stage of the plasmodium parasite) and they are relatively old, as they need to survive the development period of the mal ...201525888982
anopheles gambiae eicosanoids modulate plasmodium berghei survival from oocyst to salivary gland invasion.eicosanoids affect the immunity of several pathogen/insect models, but their role on the anopheles gambiae response to plasmodium is still unknown. plasmodium berghei-infected mosquitoes were injected with an eicosanoid biosynthesis inhibitor, indomethacin (in), or a substrate, arachidonic acid (aa), at day 7 or day 12 post-infection (p.i.). salivary gland invasion was evaluated by sporozoite counts at day 21 p.i. in promoted infection upon sporozoite release from oocysts, but inhibited infectio ...201425141285
anopheles gambiae blood feeding initiates an anticipatory defense response to plasmodium berghei.mosquitoes have potent innate defense mechanisms that protect them from infection by diverse pathogens. much remains unknown about how different pathogens are sensed and specific responses triggered. leucine-rich repeat immune proteins (lrims) are a mosquito-specific family of putative innate receptors. although some lrims have been implicated in mosquito immune responses, the function of most family members is largely unknown. we screened anopheles gambiae lrims by rnai for effects on mosquito ...201425247883
novel factors of anopheles gambiae haemocyte immune response to plasmodium berghei infection.insect haemocytes mediate cellular immune responses (e.g., phagocytosis) and contribute to the synthesis of humoral immune factors. in previous work, a genome-wide molecular characterization of anopheles gambiae circulating haemocytes was followed by functional gene characterization using cell-based rnai screens. assays were carried out to investigate the role of selected haemocyte-specific or enriched genes in phagocytosis of bacterial bio-particles, expression of the antimicrobial peptide cecr ...201626858200
a serine protease homolog negatively regulates tep1 consumption in systemic infections of the malaria vector anopheles gambiae.clip domain serine protease homologs are widely distributed in insect genomes and play important roles in regulating insect immune responses, yet their exact functions remain poorly understood. here, we show that clipa2, a clip domain serine protease homolog of anopheles gambiae, regulates the consumption of the mosquito complement-like protein tep1 during systemic bacterial infections. we provide evidence that clipa2 localizes to microbial surfaces in a tep1-dependent manner whereby it negative ...201425012124
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
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
characterization of plasmodium developmental transcriptomes in anopheles gambiae midgut reveals novel regulators of malaria transmission.the passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. here, we used dna microarrays to profile the developmental transcriptomes of the rodent malaria parasite plasmodium berghei in vivo, in the midgut of anopheles gambiae mosquitoes, from parasite stages in the midgut blood bolus to sporulating oocysts on the basal gut wall. data analysis identified several distinct transcriptional programmes en ...201425225164
wild anopheles funestus mosquito genotypes are permissive for infection with the rodent malaria parasite, plasmodium berghei.malaria parasites undergo complex developmental transitions within the mosquito vector. a commonly used laboratory model for studies of mosquito-malaria interaction is the rodent parasite, p. berghei. anopheles funestus is a major malaria vector in sub-saharan africa but has received less attention than the sympatric species, anopheles gambiae. the imminent completion of the a. funestus genome sequence will provide currently lacking molecular tools to describe malaria parasite interactions in th ...201323593423
engineered single nucleotide polymorphisms in the mosquito mek docking site alter plasmodium berghei development in anopheles gambiae.susceptibility to plasmodium infection in anopheles gambiae has been proposed to result from naturally occurring polymorphisms that alter the strength of endogenous innate defenses. despite the fact that some of these mutations are known to introduce non-synonymous substitutions in coding sequences, these mutations have largely been used to rationalize knockdown of associated target proteins to query the effects on parasite development in the mosquito host. here, we assay the effects of engineer ...201424957684
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
an epithelial serine protease, agesp, is required for plasmodium invasion in the mosquito anopheles gambiae.plasmodium parasites need to cross the midgut and salivary gland epithelia to complete their life cycle in the mosquito. however, our understanding of the molecular mechanism and the mosquito genes that participate in this process is still very limited.201222509400
alternative splicing of the anopheles gambiae dscam gene in diverse plasmodium falciparum infections.in insects, including anopheles mosquitoes, dscam (down syndrome cell adhesion molecule) appears to be involved in phagocytosis of pathogens, and shows pathogen-specific splice-form expression between divergent pathogen (or parasite) types (e.g. between bacteria and plasmodium or between plasmodium berghei and plasmodium falciparum). here, data are presented from the first study of dscam expression in response to genetic diversity within a parasite species.201121651790
a new role for an old antimicrobial: lysozyme c-1 can function to protect malaria parasites in anopheles mosquitoes.plasmodium requires an obligatory life stage in its mosquito host. the parasites encounter a number of insults while journeying through this host and have developed mechanisms to avoid host defenses. lysozymes are a family of important antimicrobial immune effectors produced by mosquitoes in response to microbial challenge.201121573077
the evolutionary divergence of stat transcription factor in different anopheles species.anopheles mosquito transmits plasmodium, the malaria causing parasite. different species of anopheles mosquito dominate in a particular geographical location and are capable of transmitting specific strains of plasmodium. it is important to understand the biology of different anophelines to control the parasite transmission. stat is an evolutionary conserved transcription factor that regulates the parasite development in african malaria vector anopheles gambiae. unlike drosophila and aedes aegyp ...201727664587
a possible key molecule for the invasion of the plasmodium berghei ookinetes into the midgut epithelium of anopheles gambiae mosquitoes.in order to identify molecules necessary for the invasion of the mosquito midgut epithelium by plasmodia, interaction assays between both these structures were devised.201020554998
plasmodium infection alters anopheles gambiae detoxification gene expression.anopheles gambiae has been shown to change its global gene expression patterns upon plasmodium infection. while many alterations are directly related to the mosquito's innate immune response, parasite invasion is also expected to generate toxic by-products such as free radicals. the current study aimed at identifying which loci coding for detoxification enzymes are differentially expressed as a function of plasmodium berghei infection in midgut and fat body tissues.201020482856
mosquito immune responses and compatibility between plasmodium parasites and anopheline mosquitoes.functional screens based on dsrna-mediated gene silencing identified several anopheles gambiae genes that limit plasmodium berghei infection. however, some of the genes identified in these screens have no effect on the human malaria parasite plasmodium falciparum; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different plasmodium species.200919643026
two c-type lectins cooperate to defend anopheles gambiae against gram-negative bacteria.c-type lectins (ctls) are a family of proteins that share a common structural motif, the carbohydrate recognition domain, and may act as receptors in pathogen recognition. indeed, some vertebrate ctls, particularly the collectins, are unequivocally implicated in the innate immune response to certain microbes. although studies in insects and other invertebrates have described ctl activation of effector immune responses in vitro, the contribution of these ctls to immune defenses in vivo is still p ...200919380589
chloroquine mediated modulation of anopheles gambiae gene expression.plasmodium development in the mosquito is crucial for malaria transmission and depends on the parasite's interaction with a variety of cell types and specific mosquito factors that have both positive and negative effects on infection. whereas the defensive response of the mosquito contributes to a decrease in parasite numbers during these stages, some components of the blood meal are known to favor infection, potentiating the risk of increased transmission. the presence of the antimalarial drug ...200818596975
the parasite invasion marker srpn6 reduces sporozoite numbers in salivary glands of anopheles gambiae.for malaria transmission to occur, plasmodium sporozoites must infect the salivary glands of their mosquito vectors. this study reports that anopheles gambiae srpn6 participates in a local salivary gland epithelial response against the rodent malaria parasite, plasmodium berghei. we showed previously that srpn6, an immune inducible midgut invasion marker, influences ookinete development. here we report that srpn6 is also specifically induced in salivary glands with the onset of sporozoite invasi ...200818005239
clip proteases and plasmodium melanization in anopheles gambiae.melanization is a potent immune response mediated by phenoloxidase (po). multiple clip-domain serine proteases (clip) regulate po activation as part of a complex cascade of proteases that are cleaved sequentially. the role of several clip as key activators or suppressors of the melanization responses of anopheles gambiae to plasmodium berghei (murine malaria) has been established recently using a genome-wide reverse genetics approach. important differences in regulation of po activation between ...200717512801
increased melanizing activity in anopheles gambiae does not affect development of plasmodium falciparum.serpins are central to the modulation of various innate immune responses in insects and are suspected to influence the outcome of malaria parasite infection in mosquito vectors. three anopheles gambiae serpins (srpn1, -2, and -3) were tested for their ability to inhibit the prophenoloxidase cascade, a key regulatory process in the melanization response. recombinant srpn1 and -2 can bind and inhibit a heterologous phenoloxidase-activating protease and inhibit phenoloxidase activation in vitro. us ...200617065316
sage analysis of mosquito salivary gland transcriptomes during plasmodium invasion.invasion of the vector salivary glands by plasmodium is a critical step for malaria transmission. to describe salivary gland cellular responses to sporozoite invasion, we have undertaken the analysis of anopheles gambiae salivary gland transcriptome using serial analysis of gene expression (sage). statistical analysis of the more than 160000 sequenced tags generated from four libraries, two from glands infected by plasmodium berghei, two from glands of controls, revealed that at least 57 anophel ...200717054438
boosting nf-kappab-dependent basal immunity of anopheles gambiae aborts development of plasmodium berghei.anopheles gambiae, the major vector for the protozoan malaria parasite plasmodium falciparum, mounts powerful antiparasitic responses that cause marked parasite loss during midgut invasion. here, we showed that these antiparasitic defenses were composed of pre- and postinvasion phases and that the preinvasion phase was predominantly regulated by rel1 and rel2 members of the nf-kappab transcription factors. concurrent silencing of rel1 and rel2 decreased the basal expression of the major antipara ...200617045818
plasmodium berghei ookinetes bind to anopheles gambiae and drosophila melanogaster annexins.using a proteomic approach we identified polypeptides from anopheles gambiae and drosophila melanogaster protein extracts that selectively bind purified plasmodium berghei ookinetes in vitro; these were two and three distinct polypeptides, respectively, with an apparent molecular weight of about 36 kda. combining two-dimensional electrophoresis and maldi-tof (matrix-associated laser desorption ionization time of flight) mass spectrometry we determined that the polypeptides correspond to isomorph ...200515948958
driving midgut-specific expression and secretion of a foreign protein in transgenic mosquitoes with agaper1 regulatory elements.the anopheles gambiae adult peritrophic matrix protein 1 (agaper1) regulatory elements were used to drive the expression of phospholipase a2 (pla2), a protein known to disrupt malaria parasite development in mosquitoes. these agaper1 regulatory elements were sufficient to promote the accumulation of pla2 in midgut epithelial cells before a blood meal and its release into the lumen upon blood ingestion. plasmodium berghei oocyst formation was reduced by approximately 80% (74-91% range) in transge ...200515926896
inducible peroxidases mediate nitration of anopheles midgut cells undergoing apoptosis in response to plasmodium invasion.plasmodium berghei invasion of anopheles stephensi midgut cells causes severe damage, induces expression of nitric-oxide synthase, and leads to apoptosis. the present study indicates that invasion results in tyrosine nitration, catalyzed as a two-step reaction in which nitric-oxide synthase induction is followed by increased peroxidase activity. ookinete invasion induced localized expression of peroxidase enzymes, which catalyzed protein nitration in vitro in the presence of nitrite and h(2)o(2) ...200415456781
bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes.malaria kills millions of people every year, and new control measures are urgently needed. the recent demonstration that (effector) genes can be introduced into the mosquito germ line to diminish their ability to transmit the malaria parasite offers new hope toward the fight of the disease (ito, j., ghosh, a., moreira, l. a., wimmer, e. a. & jacobs-lorena, m. (2002) nature, 417, 452-455). because of the high selection pressure that an effector gene imposes on the parasite population, development ...200212167627
gambicin: a novel immune responsive antimicrobial peptide from the malaria vector anopheles gambiae.a novel mosquito antimicrobial peptide, gambicin, and the corresponding gene were isolated in parallel through differential display-pcr, an expressed sequence tag (est) project, and characterization of an antimicrobial activity in a mosquito cell line by reverse-phase chromatography. the 616-bp gambicin orf encodes an 81-residue protein that is processed and secreted as a 61-aa mature peptide containing eight cysteines engaged in four disulfide bridges. gambicin lacks sequence homology with othe ...200111606751
plasmodium berghei: selection of mefloquine-resistant parasites through drug pressure in mosquitoes.mefloquine is an antimalarial drug with schizonticidal activity on blood-stage parasites. studies of the role of mefloquine on the development of plasmodium berghei anka in anopheles stephensi have been carried out that showed a dose-dependent effect on the sporogonic cycle of these parasites, with changes in the numbers of oocysts and the extent of sporozoite invasion of salivary glands. in this study, we show that mefloquine-resistant p. berghei anka blood stage parasites could be selected thr ...19957628567
innexin agap001476 is critical for mediating anti-plasmodium responses in anopheles mosquitoes.the toll and imd pathways are known to be induced upon plasmodium berghei and plasmodium falciparum infection, respectively. it is unclear how plasmodium or other pathogens in the blood meal and their invasion of the midgut epithelium would trigger the innate immune responses in immune cells, in particular hemocytes. gap junctions, which can mediate both cell-to-cell and cell-to-extracellular communication, may participate in this signal transduction. this study examined whether innexins, gap ju ...201425035430
in depth annotation of the anopheles gambiae mosquito midgut transcriptome.genome sequencing of anopheles gambiae was completed more than ten years ago and has accelerated research on malaria transmission. however, annotation needs to be refined and verified experimentally, as most predicted transcripts have been identified by comparative analysis with genomes from other species. the mosquito midgut-the first organ to interact with plasmodium parasites-mounts effective antiplasmodial responses that limit parasite survival and disease transmission. high-throughput illum ...201425073905
hemozoin activates the innate immune system and reduces plasmodium berghei infection in anopheles gambiae.malaria is a worldwide infectious disease caused by plasmodium parasites and transmitted by female anopheles mosquitoes. the malaria vector mosquito anopheles can trigger effective mechanisms to control completion of the plasmodium lifecycle; the mosquito immune response to the parasite involves several pathways which are not yet well characterized. plasmodium metabolite hemozoin has emerged as a potent immunostimulator of mammalian tissues. in this study, we aim to investigate the role of this ...201525573379
transcriptome-wide analysis of microrna expression in the malaria mosquito anopheles gambiae.micrornas (mirnas) are a highly abundant class of small noncoding regulatory rnas that post-transcriptionally regulate gene expression in multicellular organisms. mirnas are involved in a wide range of biological and physiological processes, including the regulation of host immune responses to microbial infections. small-scale studies of mirna expression in the malaria mosquito anopheles gambiae have been reported, however no comprehensive analysis of mirnas has been performed so far.201424997592
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
anopheles midgut frep1 mediates plasmodium invasion.malaria transmission depends on sexual stage plasmodium parasites successfully invading anopheline mosquito midguts following a blood meal. however, the molecular mechanisms of plasmodium invasion of mosquito midguts have not been fully elucidated. previously, we showed that genetic polymorphisms in the fibrinogen-related protein 1 (frep1) gene are significantly associated with plasmodium falciparum infection in anopheles gambiae, and frep1 is important for plasmodium berghei infection of mosqui ...201525991725
anopheles stephensi heme peroxidase hpx15 suppresses midgut immunity to support plasmodium development.the heme peroxidase hpx15 is an evolutionary conserved anopheline lineage-specific gene. previously, we found that this gene is present in the genome of 19 worldwide distributed different species of anopheles mosquito and its orthologs are absent in other mosquitoes, insects, or human. in addition, 65-99% amino acid identity among these 19 orthologs permitted us to hypothesize that the functional aspects of this gene might be also conserved in different anophelines. in this study, we found that ...201728352267
the plasmodium falciparum cell-traversal protein for ookinetes and sporozoites as a candidate for preerythrocytic and transmission-blocking vaccines.recent studies have shown that immune responses against the cell-traversal protein for plasmodium ookinetes and sporozoites (celtos) can inhibit parasite infection. while these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the plasmodium falciparum celtos in vivo using a newly developed rodent malaria chimeric parasite expressing the p. falciparum celtos (pfceltos), we evaluated the protective ...201727895131
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