Studniberg Stephanie I, Bafit Mariam, Ioannidis Lisa J, Worley Matthew J, Trianty Leily, Utami Retno A S, Puspitasari Agatha M, Apriyanti Dwi, Coutrier Farah N, Poespoprodjo Jeanne R, Kenangalem Enny, Andries Benediktus, Prayoga Pak, Price Ric N, Noviyanti Rintis, Garnham Alexandra L, Hansen Diana S
Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, Australia.
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Mol Syst Biol. 2025 Aug 19. doi: 10.1038/s44320-025-00135-z.
Although asymptomatic malaria was historically perceived as innocuous, emerging evidence revealed an immunosuppressive signature induced by asymptomatic Plasmodium falciparum infections. To examine if a similar process occurs in Plasmodium vivax malaria, we pursued a systems approach, integrating transcriptional profiling together with previously reported and novel mass cytometry phenotypes from individuals with symptomatic and asymptomatic P. vivax malaria. Symptomatic P. vivax malaria featured upregulation of anti-inflammatory pathways and checkpoint receptors. A profound downregulation of transcripts with roles in monocyte function was observed in symptomatic P. vivax malaria. This reduction in monocyte transcriptional activity was accompanied by a significant depletion of CCR2CXCR4 classical monocytes in symptomatic individuals. Despite allowing transcriptional profiles supporting T-cell differentiation, dysregulation of genes associated with monocyte activation and the inflammasome was also evident in individuals carrying P. vivax asymptomatic infections. Our results identify monocyte dysregulation as a key feature of the response to P. vivax malaria and support the concept that asymptomatic infection is not innocuous and might not support all immune processes required to eliminate parasitemia or efficiently respond to vaccination.
尽管无症状疟疾在历史上被认为是无害的，但新出现的证据显示，无症状恶性疟原虫感染会引发一种免疫抑制特征。为了研究间日疟原虫疟疾是否会发生类似过程，我们采用了一种系统方法，将转录谱分析与先前报道的以及来自有症状和无症状间日疟原虫疟疾患者的新的质谱流式细胞术表型相结合。有症状的间日疟原虫疟疾具有抗炎途径和检查点受体的上调。在有症状的间日疟原虫疟疾中，观察到在单核细胞功能中起作用的转录本显著下调。在有症状个体中，单核细胞转录活性的这种降低伴随着CCR2CXCR4经典单核细胞的显著减少。尽管允许转录谱支持T细胞分化，但在携带间日疟原虫无症状感染的个体中，与单核细胞活化和炎性小体相关的基因失调也很明显。我们的结果确定单核细胞失调是对间日疟原虫疟疾反应的一个关键特征，并支持无症状感染并非无害且可能无法支持消除寄生虫血症或有效应对疫苗接种所需的所有免疫过程这一概念。
