Project description:Plasmodium berghei ANKA infection in mice is used as a model for human cerebral malaria, the most severe complication of Plasmodium falciparum infection. The response of brain cells such as microglia has been little investigated, and may play a role in the pathogenesis or regulation of cerebral malaria. We showed previously that microglia are activated in P. berghei infections, and that Type 1 Interferon signaling is important for activation. This dataset contains the transcriptome of brain microglia of infected mice in the presence and absence of Type I interferon signaling, with the aim of identifying the genes involved in this pathway in microglia during experimental cerebral malaria. Refererence: Capuccini et al 2016, Scientific Reports, 6:39258 The global gene expression profiles from RNA of microglia isolated from uninfected and P berghei-infected wild-type C57BL/6 mice and and IFNA Receptor Knock-out mice using Illumina Beadarrays.
Project description:Malaria infection induces complex and diverse immune responses, including impairment of dendritic cell (DC) function and immune suppression that may contribute to the low vaccination antibody titers to some antigens in endemic populations. To elucidate the mechanisms underlying host-parasite interaction, we performed a genetic screen during early Plasmodium yoelii infection and identified a large number of interacting host and parasite genes/loci after trans-species expression quantitative trait loci (Ts-eQTL) analysis. We next investigated a host E3 ubiquitin ligase gene (march1) that was clustered with interferon stimulated genes. March1 can inhibit MAVS/STING induced IFN-I signaling and reverse inhibition of viral replication mediated by MAVS in vitro. However, in malaria-infected hosts, deficiency of march1 activates IFN signaling inhibitors such as SOCS1, SOCS3, and TRIM24, leading to reduced early (24h) serum IFN-I levels. Increased CD86+ DC populations and elevated levels of IFN-? and IL-10 produced by T cells day 4 post infection protect infected march1-/- mice. Malaria lysate stimulate MACRH1 expression, which reduces CD86+ DC cells and impairs T cell activation. This study reveals previous unknown functions of MARCH1 in innate response to malaria infections and provides potential avenues for activating anti-malaria immunity and enhancing vaccine efficacy.
