Journal
GENES AND IMMUNITY
Volume 21, Issue 1, Pages 45-62Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41435-019-0085-9
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Funding
- ARCir Dynamique Region Nord-Pas de Calais
- LabEx PARAFRAP [ANR-11-LABX0024]
- PRESTIGE [2014-1-0043: Marie Curie Actions/FP7/PCOFUND-GA-2013-609102]
- Region Haut-de-France (CNRS) [147894]
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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 Berr2(WLA) 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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