Anopheles gambiae immune responses to human and rodent Plasmodium parasite species
Ontology highlight
ABSTRACT:
ORGANISM(S): Anopheles gambiae
PROVIDER: GSE8789 | GEO | 2007/08/15
SECONDARY ACCESSION(S): PRJNA102089
REPOSITORIES: GEO
Similar Datasets
Project description:Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito’s immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. By comparing gene expression patterns between carcassess or guts of mosquitoes that fed on a P. falciparum or P. berghei wt and mosquitoes that fed on invasion incapable strains we gain information on the A. gambiae transcriptional responses to the invading ookinete at 24 hours after feeding. By comparing gene expression patterns between carcassess or guts of mosquitoes that fed on a P. falciparum ookinete invasion incapable strain and mosquitoes that fed on non-infected blood we gain information on the A. gambiae transcriptional responses to malaria infected blood in absence of ookinete invasion at 24 hours after feeding. By comparing gene expression patterns between mosquitoes at 4 hours after being injected with either E. coli or S. aureus and mosquitoes injected with sterile PBS we gain information on the mosquito's transcriptional response to these bacterial challenges.
2007-08-15 | E-GEOD-8789 | biostudies-arrayexpress
Project description: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 of septic and aseptic mosquitoes and to determine whether bacteria-independent anti-Plasmodium defenses exist. To examine the impact of P. falciparum infection on the mosquito midgut and carcass transcriptomes in the presence or absence of midgut bacteria, we used A. gambiae whole genome microarrays to compare the mRNA abundance of P. falciparum-infected and -naïve mosquitoes of antibiotic- and non-antibiotic treated cohorts. P. falciparum infection induced changes in the abundance of as many as 2,183 and 2,429 transcripts in whole mosquitoes belonging to a variety of functional groups in aseptic and septic mosquitoes. Ultimately, we were interested in identifying the genes involved in bacteria-independent anti-Plasmodium responses, and therefore we focused on transcripts displaying increased abundance in the parasite-infected aseptic midguts, placing a particular emphasis on those with predicted immune functions. Because of the central role of serine protease cascades in regulating insect immune defenses, we focused the remainder of our analysis on a clip-domain serine protease C2 (CLIPC2, AGAP004317) and a serine protease inhibitor 7 (SRPN7, AGAP007693) that were specifically upregulated in the parasite-infected, aseptic mosquito midgut. We showed that SRPN7 negatively and CLIPC2 positively regulate the anti-Plasmodium defense, independently of the midgut-associated bacteria. Co-silencing assays suggested that these two genes may function together in a signaling cascade. Neither gene was regulated, nor modulated, by infection with the rodent malaria parasite Plasmodium berghei, suggesting that SRPN7 and CLIPC2 are components of a defense system with preferential activity towards P. falciparum. Further analysis using RNA interference determined that these genes do not regulate the anti-Plasmodium defense mediated by the IMD pathway, and both factors act as agonists of the endogenous midgut microbiota, further demonstrating the lack of functional relatedness between these genes and the bacteria-dependent activation of the IMD pathway. This is the first study confirming the existence of a bacteria-independent, anti-P. falciparum defense. Aseptic and septic midguts and carcasses from P. falciparum-infected A. gambiae vs aseptic and septic midguts and carcasses from uninfected, blood-fed A. gambiae. 3 biological replicates and 1 pseudo-replicate per each array.
2013-08-10 | E-GEOD-49690 | biostudies-arrayexpress
Project description:Malaria morbidity and mortality caused by both Plasmodium falciparum and Plasmodium vivax extend well beyond the African continent, and, although P. vivax causes 80-300 million severe cases each year, vivax transmission remains poorly understood. Plasmodium parasites are transmitted by Anopheles mosquitoes, and the critical site of interaction between parasite and host is at the mosquito's luminal midgut brush border. While the genome of the "model" African P. falciparum vector, Anopheles gambiae, has been sequenced, evolutionary divergence limits its utility as a reference across anophelines, especially non-sequenced P. vivax vectors such as Anopheles albimanus. Clearly, enabling technologies and platforms that bridge this substantial scientific gap are required in order to provide public health scientists key transcriptomic and proteomic information that could spur the development of novel interventions to combat this disease. To our knowledge, no approaches have been published which address this issue. To bolster our understanding of P. vivax-An. albimanus midgut interactions, we developed an integrated bioinformatic-hybrid RNA-Seq-LC-MS/MS approach involving An. albimanus transcriptome (15,764 contigs) and luminal midgut subproteome (9,445 proteins) assembly, which, when used with our custom Diptera protein database (685,078 sequences), facilitated a comparative proteomic analysis of the midgut brush borders of two important malaria vectors, An. gambiae and An. albimanus. Summary from: http://www.mcponline.org/content/early/2012/10/17/mcp.M112.019596.long The An. albimanus transcriptome dataset is available at http://funcgen.vectorbase.org/RNAseq/Anopheles_albimanus/INSP/v2
2012-11-02 | PXD000062 | Pride
Project description: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 of septic and aseptic mosquitoes and to determine whether bacteria-independent anti-Plasmodium defenses exist. To examine the impact of P. falciparum infection on the mosquito midgut and carcass transcriptomes in the presence or absence of midgut bacteria, we used A. gambiae whole genome microarrays to compare the mRNA abundance of P. falciparum-infected and -naïve mosquitoes of antibiotic- and non-antibiotic treated cohorts. P. falciparum infection induced changes in the abundance of as many as 2,183 and 2,429 transcripts in whole mosquitoes belonging to a variety of functional groups in aseptic and septic mosquitoes. Ultimately, we were interested in identifying the genes involved in bacteria-independent anti-Plasmodium responses, and therefore we focused on transcripts displaying increased abundance in the parasite-infected aseptic midguts, placing a particular emphasis on those with predicted immune functions. Because of the central role of serine protease cascades in regulating insect immune defenses, we focused the remainder of our analysis on a clip-domain serine protease C2 (CLIPC2, AGAP004317) and a serine protease inhibitor 7 (SRPN7, AGAP007693) that were specifically upregulated in the parasite-infected, aseptic mosquito midgut. We showed that SRPN7 negatively and CLIPC2 positively regulate the anti-Plasmodium defense, independently of the midgut-associated bacteria. Co-silencing assays suggested that these two genes may function together in a signaling cascade. Neither gene was regulated, nor modulated, by infection with the rodent malaria parasite Plasmodium berghei, suggesting that SRPN7 and CLIPC2 are components of a defense system with preferential activity towards P. falciparum. Further analysis using RNA interference determined that these genes do not regulate the anti-Plasmodium defense mediated by the IMD pathway, and both factors act as agonists of the endogenous midgut microbiota, further demonstrating the lack of functional relatedness between these genes and the bacteria-dependent activation of the IMD pathway. This is the first study confirming the existence of a bacteria-independent, anti-P. falciparum defense.
2013-08-10 | GSE49690 | GEO
Project description:A deeper understanding of malaria parasite development inside the Anopheles mosquito may lead to the identification of processes that can be targeted by transmission-blocking interventions. Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) is a potent superoxide-inducing agent that impacts Plasmodium ookinete development, especially at higher concentrations. Compounds like Paraquat can potentially induce an oxidative imbalance in the mosquito midgut during ookinete maturation, essentially super-stressing the parasite leading to the arrested development of ookinetes, the only stage that can invade through a mosquito midgut cell to establish an oocyst infection in the mosquito. The mosquito midgut has evolved to handle the natural production of reactive oxygen and nitrogen species (ROS and RNS, respectively) as a result of feeding on blood. The addition of Paraquat to a bloodmeal is expected to induce a cognate response in the midgut to handle the excess ROS/RNS, and high concentrations of this compound can potentially overwhelm the midgut response leading to mosquito death. While several studies have explored the effect of Paraquat on malaria parasites, a fundamental understanding of the mosquito response to this compound remains unknown. Here, we quantified the mosquito midgut proteomic response to a Paraquat-laced sugar meal to understand the intrinsic midgut response (in the absence of a bloodmeal). We then carried out transcriptomic analysis of the mosquito midgut for several antioxidants of the Trx and GSH pathways to compare concordance or discordance between protein and its transcripts during different oxidative stress conditions. Finally, we determined whether the same Trx and GSH pathways are upregulated following infection with either P. falciparum or P. berghei at 24 hrs post-blood feeding, coinciding with the time point for maximal ookinete traversal of the midgut. We discuss the potential selective action of Paraquat on the parasite and the intrinsic tolerance of the mosquito midgut to Paraquat-mediated oxidative stress.
2022-03-01 | PXD008231 | Pride
Project description:A general understanding of redox homeostasis in An. gambiae midgut epithelial cells under different oxidative conditions during P. falciparum ookinete invasion is missing. We used an ex vivo midgut culture model to understand AgTrx-1 protein expression pattern in An. gambiae midguts under oxidative stress of the ROS inducer, tert-butyl hydroperoxide (tBHP). We then quantified the midgut proteomic expression profile to understand organ-level regulation of the response to oxidative stress. An. gambiae midguts under low (50M) and high (200M) tBHP concentrations were enriched in ribosomal proteins (RPs), consistent with cells undergoing ribosomal/nucleolar stress. Nevertheless, these midguts were also enriched in peptidases, integral membrane proteins, and cytochrome P450s indicating cells that are undergoing protein processing and folding through post-translational modification (PTMs), and detoxification of toxic compounds through active efflux. This response to oxidative stress was strikingly dissimilar to that observed from previous studies with another dipteran, Drosophila following oxidative stress induction. Our data indicates that the response to tBHP induced oxidative stress is mild and suggests that the associated antioxidant response is similar to what is observed during midgut invasion of P. falciparum okinete. Furthermore, our data shows that ribosomal/nucleolar stress is crucial in the regulation of oxidative stress in An. gambiae midguts. Given this importance, its possible to develop mechanisms to perturb this ribosomal/nucleolar stress response in An. gambiae resulting into unmanageable levels of oxidative stress exposure to Plasmodium parasite in the midgut, yet still allowing the mosquito to survive the perturbation. Unmanageable levels of oxidative stress could result to harmful effect to the Plasmodium and eventually its death resulting into halting of its transmission.
2018-11-21 | PXD008251 | Pride
Project description:Host-derived factors are sucked into midgut of mosquitoes during natural malaria transmission, but their influence on malaria transmission is largely unknown. We reported that mouse complement C3 taken into mosquitoes significantly promoted malaria transmission either in laboratory or in field. This effect was attributed to the reduction of microbiota abundance in mosquito midgut by host-derived C3 through direct lyses the predominant symbiont bacteria Elizabethkingia anopheles. Elizabethkingia anopheles symbiont bacteria were demonstrated to be detrimental to malaria sexual stages in mosquitoes. Strikingly, the promoted effect of host C3 on malaria transmission was confirmed by laboratory mosquitoes membrane-feeding on Plasmodium falciparum. Therefore, we reveal a novel strategy of malaria parasite to utilize host complement C3 to promote its transmission, and the administration of C3 inhibitor would provide us a novel strategy to control malaria transmission.
2024-08-01 | GSE271070 | GEO
Project description:Background: 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. Results: We identified 4047 genes expressed in hemocytes, using An. gambiae genome-wide microarrays. While 279 transcripts were significantly enriched in hemocytes relative to whole adult female mosquitoes, 959 transcripts exhibited immune challenge-related regulation. The global transcriptomic responses of hemocytes to challenge with different species of bacteria and/or different stages of malaria parasite infection revealed discrete, minimally overlapping, pathogen-specific signatures of infection-responsive gene expression; 105 of these represented putative immunity-related genes including anti-Plasmodium factors. Of particular interest was the specific co-regulation of various members of the Imd and JNK immune signaling pathways during malaria parasite invasion of the mosquito midgut epithelium. Conclusion: Our genome-wide transcriptomic analysis of adult mosquito hemocytes reveals pathogen-specific signatures of gene regulation and identifies several novel candidate genes for future functional studies. In order to identify hemocyte-specific and immune-responsive transcripts, we first compared transcripts expressed in hemocytes from one day old sugar-fed mosquitoes to transcripts detected in whole mosquitoes of the same age and feeding status. This resulted in identification of the hemocyte-enriched transcriptome. We then compared hemocytes from 1 day old mosquitoes, 1 hour after immune challenge with heat-killed Escherichia coli or Micrococcus luteus, to control female mosquitoes injected with sterile PBS to determine the bacteria challenge responsive transcriptomes. We used heat-killed bacteria in these assays, because our primary interest was in identifying the bacterial responsive transcriptome and to avoid the potentially confounding effects of altered gene expression due to the lethal effects of a systemic infection associated with injection of living bacteria. Lastly, we compared hemocytes from mosquitoes at 24 hours and 19 days after ingestion of a blood meal infected with Plasmodium berghei to mosquitoes of the same age fed a non-infected blood meal to determine the ookinete and sporozoite infection responsive transcriptomes, respectively. This design resulted in a total of five experimental treatments. The following samples are not included in this submission: Hemo E coli vs. hemo unchallenged A Hemo E coli vs. hemo unchallenged B Hemo m luteus vs. hemo unchallenged A Hemo m luteus vs. hemo unchallenged B
2011-10-31 | E-GEOD-33269 | biostudies-arrayexpress
Project description:In this study we determine the effects of silencing adiponectin receptor in A. gambiae mosquitoes after taking Plasmodium gambiae infected blood meals. dsRNA (dsAdpR and dsGluc) microinjected A. gambiae mosquitoes were fed on P. berghei-infected Swiss Webster mice. Two days after a blood meal, the mosquitoes were collected for midgut dissection.
2023-11-09 | GSE198929 | GEO
Project description:Plasmodium berghei WT and ap2-o disruptant ookinete culture 12h Plasmodium berghei WT and ap2-o disruptant ookinete culture 12h
2010-05-14 | E-GEOD-14376 | biostudies-arrayexpress