Project description:Blood-stage malaria infection induces differentiation of several effector CD4 + T subsets including Tfh and Th1 cells. The cues and microarchitectural niches required in secondary lymphoid organs for their formation were previously uncharacterised. Here we used spatial transcriptomics to characterise the microarchitecture of mouse spleen before and during malaria infection, and mapping the spatial and molecular requirements of Tfh/Th1 differentiation.
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. Keywords: Human PBMC samples from natural and experimentally (clinical trial) induced malaria
Project description:Cerebral malaria (CM) is one of the most severe complications of malaria infection. There is evidence that repeated parasite exposure promotes resistance against CM, as indicated by the low incidence of CM in adults in malaria-endemic regions. However, the immunological basis of this infection-induced resistance remains poorly understood. Here, a microarray study done utilising the tractable Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we show that three rounds of infection and drug-cure protects against the development of ECM during a subsequent fourth infection.
Project description:Blood-stage malaria infection induces differentiation of several effector CD4 + T subsets including Tfh and Th1 cells. The cues and microarchitectural niches required in secondary lymphoid organs for their formation were previously uncharacterised. Here we used scRNA-seq to profile splenocyte transcriptomes at steady state or upon malaria infection as a reference dataset for deconvolution of spatial transcriptomic data.
Project description:Gene expression patterns were investigated in well-defined genetically cerebral malaria-resistant (CM-R) and cerebral malaria-susceptible (CM-S) mouse strains. cDNA microarrays were used to search for differentially expressed genes in mouse brain. Four mouse strains, known to differ in susceptibility to cerebral malaria upon Plasmodium berghei ANKA infection, were compared: BALB/c and DBA/2 mice are CM-R, while C57BL/6 and CBA/J mice are CM-S.
Project description:RTS,S is the sole candidate vaccine shown to provide protection against infection to malaria-naive adults challenged with mosquito-borne homologous falciparum malaria and protection against infection and clinical and severe disease to volunteers in malaria-endemic Africa who were exposed to diverse Plasmodium falciparum strains. In this experiment we profiled gene expression in PBMCs after vaccination with the RTS,S candidate malaria vaccine in a controlled human malaria infection study. Subjects were vaccinated with three doses of the RTS,S candidate malaria vaccine. Blood samples for PBMC isolation and subsequent gene expression analysis were taken on day 0 (0m), day of the third vaccination (8w), 1 day post third vaccination (8w1d), 3 days post third vaccination (8w3d), the day of the infection (10w), 1 day post infection (10w1d), and 5 days post infection (10w5d). After infection the subjects were closely monitored for parasitemia. The response to the controlled infection was recorded as follows: no parasitemia (P, protected), parasitemia in the same time frame as the control group (NP, not protected), parasitemia later than the control group (DL, delayed). In addition to the experimental factors, a confounding factor was identified in the data analysis related to the use of a specific kit batch (Kit A or B).
Project description:Blood-stage malaria infection induces differentiation of several effector CD4 + T subsets including Tfh and Th1 cells. The cues and microarchitectural niches required in secondary lymphoid organs for their formation were previously uncharacterised. Here we used scRNA-seq to profile CD4+ T cell transcriptomes upon malaria infection as a reference dataset for deconvolution of spatial transcriptomic data.
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.
