Gene Expression Analysis in Malaria Infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE5418 | GEO | 2006/10/01
SECONDARY ACCESSION(S): PRJNA96239
REPOSITORIES: GEO
Similar Datasets
Project description:Using genome-wide expression profiles from persons either experimentally challenged with malaria-infected mosquitoes or naturally-infected with Plasmodium falciparum malaria, we present details of the transcriptional changes that occur with infection and that are either commonly shared between subjects with pre-symptomatic and clinically apparent malaria or that distinguish these two groups. Our findings confirm and extend aspects of the earliest responses to malaria infection at the molecular level and which may be informative in elucidating how innate and adaptive immune responses may be modulated in different stages of infection. Experiment Overall Design: Compared samples from patients with naturally acquired malaria infection to those from volunteers in a challenge model vaccine trial.
2007-11-01 | E-GEOD-5418 | biostudies-arrayexpress
Project description:Malaria, caused by Plasmodium parasites is responsible for the illness of millions of individuals each year. Plasmodium sporozoites inoculated by mosquitoes migrate to the liver and infect hepatocytes prior to release of merozoites that initiate symptomatic blood-stage malaria. Parasites are thought to be restricted to hepatocytes throughout this obligate liver-stage of replication and differentiation. In contrast to this notion, we found that a subset of hepatic dendritic CD11c+ cells co-expressing F4/80, CD103, CD207 and CSF1R, acquired a substantial parasite burden during the liver-stage of malaria, but only after initial hepatocyte infection. These CD11c+ cells found in the infected liver and liver-draining lymph nodes exhibited transcriptionally and phenotypically enhanced antigen-presentation functions; and primed protective CD8 T cell responses against Plasmodium liver-stage restricted antigens. Our findings uncover a novel aspect of Plasmodium biology as well as the fundamental mechanism by which CD8 T cell responses are primed against liver-stage malaria.
2019-02-05 | GSE126110 | GEO
Project description:The goal of OOCYSTOP is based on an innovative concept to block malaria transmission by development of new drugs that will be delivered (1) to oocysts in infected mosquitoes and (2) to early stages in human infection by the sporozoite
2023-02-28 | MSV000091377 | MassIVE
Project description:Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by ATAC-seq in laboratory-reared An. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that annotate to mosquito immune-response genes. This study is important not only for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but also the information we produced is of great potential for developing new mosquito-control and anti-malaria strategies.
2020-12-22 | GSE152924 | GEO
Project description:<p>Description:<br/> Experimental exposure to malaria parasites can lead to development of protective immunity, providing a foothold for the development of a malaria vaccine. The goal of this study is to investigate immune transcriptional profiles associated with malaria protective immune responses induced by experimental Chemo-Prophylaxis and Sporozoites (CPS) immunization of P. <i>falciparum</i>-naive human volunteers. Samples for this study were obtained from a CPS-immunization study conducted in 2011 (ClinicalTrials.gov Identifier: NCT01218893), where healthy volunteers received CPS-immunization with bites from different numbers of P. <i>falciparum</i>-infected mosquitoes (three times 15 (n=5), 10 (n=9) or 5 (n=10)). Five control subjects received uninfected mosquito bites under chloroquine prophylaxis. Fifteen weeks after discontinuation of chloroquine prophylaxis, all volunteers were challenged by exposure to infected mosquito bites. </p> <p>Study Design:<br/> A maximum of 30 volunteers were divided into four groups. All volunteers received weekly chloroquine prophylaxis for a period of 13 weeks (91 days). During these 13 weeks, on days 8, 36 and 64 they were exposed to the bites of 15 mosquitoes. Group 1 (n=5, positive control) received three CPS immunizations by 15 mosquitoes infected with P. falciparum sporozoites. Group 2 (n=10) received three times 10 bites from infected mosquitoes and 5 bites from uninfected mosquitoes. Group 3 (n=10) received three times 5 bites from infected mosquitoes and 10 bites from uninfected mosquitoes. Group 4 (n=5), the negative control, received three placebo immunizations with 15 bites of uninfected mosquitoes. Fifteen weeks after discontinuation of chloroquine prophylaxis, all 30 volunteers were challenged at day 196 by the bites of 5 infectious mosquitoes and followed for 21 days. All subjects were treated with chloroquine 21 days after challenge or whenever they had a positive thick smear during that period. </p>
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Project description:To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T cell function, and CTLA-4 as a predicted regulator in these processes.
2022-02-21 | GSE181179 | GEO
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:Transcriptional responses in the gut of the main malaria vector Anopheles gambiae following oral bacterial infection with the entomopathogen Serratia marcescens were identified using DNA microarrays. S. marcescens is a common member of the mosquito gut microbiota, found in both laboratory reared and field collected mosquitoes, that can be potentially pathogenic as in Drosophila (Nehme et al., 2007), while it has been shown to influence the outcome of Plasmodium infections (Bando et al., 2013). S. marcescens belongs to the Enterobacteriaceae family, members of which have been shown to influence malaria transmission dynamics (Cirimotich et al., 2011, Boissiere et al., 2012). To further investigate the interactions between S. marcescens and the mosquito host, likely to shape, directly or indirectly, malaria transmission dynamics, An. gambiae mosquitoes, from the recently established N'gousso M form laboratory colony that retains much of the genetic variation of field mosquitoes, were antibiotic treated for 5 days and subsequently orally infected with the Db11-GFP strain of S. marcescens. Bacteria-fed mosquitoes were selected 2 days post infection, and, 3 days post infection, guts from bacteria-fed mosquitoes were dissected. Uninfected control mosquitoes were treated in the same way. Differential expression in the gut of S. marcescens infected mosquitoes, compared to uninfected controls, was identified by hybridizing labelled complementary RNA, derived from total RNA extracted from the respective gut pools, in customized Agilent 4x44k gene expression microarrays, comprising oligonucleotide probes encompassing all An. gambiae annotated genes of the AgamP3.6 release, with each probe represented in duplicate.
2013-11-30 | E-MEXP-3952 | biostudies-arrayexpress
Project description:Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within red blood cells (RBCs), thereby hiding themselves from direct contact and recognition by host immune cells. Host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been elusive. Here we investigated mouse genome-wide transcriptional responses to infections with two strains of Plasmodium yoelii (N67 and N67C) and discovered differences in innate response pathways corresponding to strain-specific disease phenotypes. Using in vitro RNAi gene knockdown and knockout mice, we demonstrated that a strong IFN-I response triggered by RNA Polymerase III and melanoma differentiation-associated protein 5 (MDA5), not Toll-like receptors (TLRs), binding of parasite DNA/RNA contributed to a decline of parasitemia in N67-infected mice. We showed that conventional dendritic cells were the major sources of early IFN-I, and that surface expression of phosphatidylserine (PS) on infected RBC (iRBC) might promote their phagocytic uptake, leading to the release of parasite ligands and the IFN-I response in N67 infection. In contrast, an elevated inflammatory response mediated by CD14/TLR and p38 signaling played a role in disease severity and early host death in N67C-infected mice. In addition to identifying cytosolic DNA/RNA sensors and signaling pathways previously unrecognized in malaria infection, our study demonstrates the importance of parasite genetic backgrounds in malaria pathology and provides important information for studying human malaria pathogenesis. Spleen RNA from mice, 4 days post infection with Plasmodium yoelii (strain N67 or N67C), or mock infection (N). Replicates from 6 individual mice per condition.
2014-01-13 | E-GEOD-51329 | biostudies-arrayexpress
Project description:Analysis of the effect of malaria infection on whole blood gene expression and uncovering regulatory effects using eQTL analysis. Testing for relashionships between genotype, expression and malaria phenotypes. We generated whole blood gene expression profiles and genotypes from 155 West-African children including 94 cases undergoing the symptomatic phase of blood-stage Plasmodium falciparum infection and 61 age-matched controls. PCA, analysis of covariance and eQTL analysis were performed on the data.
2012-09-04 | E-GEOD-34404 | biostudies-arrayexpress