Division of Infectious Diseases, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Division of Infectious Diseases, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, South Stockholm Hospital, Stockholm, Sweden.
Cell Rep. 2022 Apr 19;39(3):110709. doi: 10.1016/j.celrep.2022.110709.
Natural immunity to malaria develops over time with repeated malaria episodes, but protection against severe malaria and immune regulation limiting immunopathology, called tolerance, develops more rapidly. Here, we comprehensively profile the blood immune system in patients, with or without prior malaria exposure, over 1 year after acute symptomatic Plasmodium falciparum malaria. Using a data-driven analysis approach to describe the immune landscape over time, we show that a dampened inflammatory response is associated with reduced γδ T cell expansion, early expansion of CD16 monocytes, and parasite-specific antibodies of IgG1 and IgG3 isotypes. This also coincided with reduced parasitemia and duration of hospitalization. Our data indicate that antibody-mediated phagocytosis during the blood stage infection leads to lower parasitemia and less inflammatory response with reduced γδ T cell expansion. This enhanced control and reduced inflammation points to a potential mechanism on how tolerance is established following repeated malaria exposure.
疟疾的自然免疫力随着反复感染疟疾而逐渐产生，但对严重疟疾的保护和免疫调节限制免疫病理学，即耐受性，会更快地产生。在这里，我们全面描绘了急性症状性恶性疟原虫疟疾后 1 年有或无先前疟疾暴露的患者的血液免疫系统。我们使用数据驱动的分析方法来描述随时间变化的免疫景观，结果表明，炎症反应减弱与 γδ T 细胞扩增减少、CD16 单核细胞早期扩增以及寄生虫特异性 IgG1 和 IgG3 同种型抗体有关。这也与寄生虫减少和住院时间缩短相一致。我们的数据表明，在血液阶段感染期间抗体介导的吞噬作用会导致寄生虫减少和炎症反应减弱，γδ T 细胞扩增减少。这种增强的控制和减少的炎症表明，在反复疟疾暴露后，耐受性是如何建立的潜在机制。
