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.

中文翻译：

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小胶质细胞表达CD300lf通过阻止神经发炎而有助于抵抗脑疟疾。

遗传作图和全基因组研究为多种遗传多态性与疟疾（一种具有多种严重程度的复杂病理疾病）的关联提供了证据。我们先前已将Berr1和Berr2描述为在WLA / Pas近交小鼠品系中鉴定的候选基因，这些品系易受伯氏疟原虫ANKA诱导的对脑疟疾（CM）的抵抗。我们在这项研究中报告了我们为C57BL / 6JR（B6）背景上的Berr2WLA等位基因衍生的同系菌株的表型和功能特征。与C57BL / 6JR易感小鼠相比，发现B6.WLA-Berr2对CM具有高度抗性。通过结合基因型，转录组学和免疫应答研究，分析了与CM抗性相关的机制。我们找到了B6。与B6相比，WLA-Berr2小鼠显示出降低的寄生虫螯合和血脑屏障破坏，脑中CXCR3 + T细胞浸润低，并且对伯氏疟原虫ANKA感染后神经胶质细胞反应改变。另外，我们已经鉴定出属于Ig样编码基因家族的CD300f是与CM抗性相关的潜在候选基因。与CMS小鼠相比，从感染B6.WLA-Berr2小鼠的大脑中分离出的小胶质细胞显着表达更高水平的CD300f，并与炎症反应的抑制有关。