■先天免疫对于减轻寄生虫负担和促进严重疟疾的生存至关重要。单核细胞是先天反应的关键参与者,像巨噬细胞一样,是塑料细胞,其功能和表型受到来自微环境的信号调节。在脑型疟疾(CM)的背景下,单核细胞反应构成一个重要的问题来理解。我们先前证明,非经典单核细胞百分比的降低与CM儿童的死亡结局有关。在目前的研究中,我们推测单核细胞吞噬功能受疟疾感染严重程度的影响.
■为了研究这一假设,我们比较了贝宁患有非复杂性疟疾(UM)和CM的儿童循环单核细胞的调理和非调理吞噬能力。对于CM组,在包含时(D0)和处理后3天和30天(D3,D30)获得样品。单核细胞及其亚群的吞噬能力通过流式细胞术和转录谱分析来表征,方法是研究已知其在感染的红细胞(iRBC)消除或免疫逃逸中的功能意义的基因。
■我们的结果证实了我们的假设,并强调了非经典单核细胞吞噬iRBC的更高能力。我们还证实,与UM相比,低数量的非经典单核细胞与CM结果相关,提示这个亚群动员到大脑炎症部位。最后,我们的结果提示抑制性受体LILRB1,LILRB2和Tim3在吞噬作用控制中的作用.
■放在一起,这些数据提供了更好地了解单核细胞和疟疾感染在CM致病性中的相互作用。
UNASSIGNED: Innate immunity is crucial to reducing parasite burden and contributing to survival in severe malaria. Monocytes are key actors in the innate response and, like macrophages, are plastic cells whose function and phenotype are regulated by the signals from the microenvironment. In the context of cerebral malaria (CM), monocyte response constitutes an important issue to understand. We previously demonstrated that decreased percentages of nonclassical monocytes were associated with death outcomes in CM children. In the current study, we postulated that monocyte phagocytosis function is impacted by the severity of malaria infection.
UNASSIGNED: To study this hypothesis, we compared the opsonic and nonopsonic phagocytosis capacity of circulant monocytes from Beninese children with uncomplicated malaria (UM) and CM. For the CM group, samples were obtained at inclusion (D0) and 3 and 30 days after treatment (D3, D30). The phagocytosis capacity of monocytes and their subsets was characterized by flow cytometry and transcriptional profiling by studying genes known for their functional implication in infected-red blood cell (iRBC) elimination or immune escape.
UNASSIGNED: Our results confirm our hypothesis and highlight the higher capacity of nonclassical monocytes to phagocyte iRBC. We also confirm that a low number of nonclassical monocytes is associated with CM outcome when compared to UM, suggesting a mobilization of this subpopulation to the cerebral inflammatory site. Finally, our results suggest the implication of the inhibitory receptors LILRB1, LILRB2, and Tim3 in phagocytosis control.
UNASSIGNED: Taken together, these data provide a better understanding of the interplay between monocytes and malaria infection in the pathogenicity of CM.