Highlights • In silico analysis suggests that primary infection with P. vivax induces potent immunosuppression mediated by dendritic cells. • Antigen presentation is attenuated in malaria-experienced vs malaria-naïve individuals • Malaria induce immunosuppressive effect manifested with strong induction of IDO1 . Summary Objectives To dissect the transcriptional networks underpinning immune cells responses during primary Plasmodium vivax infection of healthy human adults. Methods We conducted network co-expression analysis of next-generation RNA sequencing data from whole blood from P. vivax and P. falciparum controlled human malaria infection (CHMI) of healthy naïve and malaria-exposed volunteers. Single cell transcription signatures were used to deconvolute the bulk RNA-Seq data into cell-specific signals. Results Initial exposure to P. vivax induced activation of innate immunity, including efficient antigen presentation and complement activation. However, this effect was accompanied by strong immunosuppression mediated by dendritic cells via the induction of Indoleamine 2,3-Dioxygenase 1(IDO1) and Lymphocyte Activation Gene 3 (LAG3). Additionally, P. vivax induced depletion of neutrophil populations associated with down regulation of 3G-protein coupled receptors, CRXCR1, CXCR2 and CSF3R. Accordingly, in malaria-exposed volunteers the inflammatory response was attenuated, with a decreased class II antigen presentation in dendritic cells. While the immunosuppressive signalling was maintained between plasmodium species, response to P. falciparum was significantly more immunogenic. Conclusions In silico analyses suggest that primary infection with P. vivax induces potent immunosuppression mediated by dendritic cells, conditioning subsequent anti-malarial immune responses. Targeting immune evasion mechanisms could be an effective alternative for improving vaccine efficacy.
【저자키워드】 Vaccines, transcriptomics, dendritic cells, malaria, immunoregulation, Controlled human malaria infection,