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Abstract
Genetic mapping and genome-wide studies provide evidence for the association of several genetic polymorphisms with malaria, a complex pathological disease with multiple severity degrees. We have previously described Berr1and Berr2 as candidate genes identified in the WLA/Pas inbreed mouse strain predisposing to resistance to cerebral malaria (CM) induced by P. berghei ANKA. We report in this study the phenotypic and functional characteristics of a congenic strain we have derived for Berr2WLA allele on the C57BL/6JR (B6) background. B6.WLA-Berr2 was found highly resistant to CM compared to C57BL/6JR susceptible mice. The mechanisms associated with CM resistance were analyzed by combining genotype, transcriptomic and immune response studies. We found that B6.WLA-Berr2 mice showed a reduced parasite sequestration and blood–brain barrier disruption with low CXCR3+ T cell infiltration in the brain along with altered glial cell response upon P. berghei ANKA infection compared to B6. In addition, we have identified the CD300f, belonging to a family of Ig-like encoding genes, as a potential candidate associated with CM resistance. Microglia cells isolated from the brain of infected B6.WLA-Berr2 mice significantly expressed higher level of CD300f compared to CMS mice and were associated with inhibition of inflammatory response.
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1 Université de Lille, Center for Infection and Immunity of Lille, CNRS UMR 8204, Inserm 1019, Institut Pasteur de Lille, Lille, France (GRID:grid.463727.3) (ISNI:0000 0004 0386 3856)
2 CIIL, Institut Pasteur de Lille, Flow Cytometry Core Facility, BioImaging Center Lille, Lille, France (GRID:grid.463727.3) (ISNI:0000 0004 0386 3856)
3 Université de Lille, Center for Infection and Immunity of Lille, CNRS UMR 8204, Inserm 1019, Institut Pasteur de Lille, Lille, France (GRID:grid.463727.3) (ISNI:0000 0004 0386 3856); UPMC/CNRS UMR 7211, Immunologie—Immunopathologie—Immunothérapie, Paris, France (GRID:grid.463727.3)