Atypical activation of dendritic cells by Plasmodium falciparum

作者：Gotz Anton^*; Tang Mei San; Ty Maureen C; Arama Charles; Ongoiba Aissata; Doumtabe Didier; Traore Boubacar; Crompton Peter D; Loke P'ng; Rodriguez Ana^*

来源：Proceedings of the National Academy of Sciences, 2017, 114(49): E10568-E10577.

DOI：10.1073/pnas.1708383114

• Plasmodium falciparum
• dendritic cells
• malaria
• activation
• cytokines

Dendritic cells (DCs) are activated by pathogens to initiate and shape immune responses. We found that the activation of DCs by Plasmodium falciparum, the main causative agent of human malaria, induces a highly unusual phenotype by which DCs up-regulate costimulatory molecules and secretion of chemokines, but not of cytokines typical of inflammatory responses (IL-1 beta, IL-6, IL-10, TNF). Similar results were obtained with DCs obtained from malaria-naive US donors and malaria-experienced donors from Mali. Contact-dependent cross-talk between the main DC subsets, plasmacytoid and myeloid DCs (mDCs) was necessary for increased chemokine and IFN-alpha secretion in response to the parasite. Despite the absence of inflammatory cytokine secretion, mDCs incubated with P. falciparum-infected erythrocytes activated antigen-specific naive CD4(+) T cells to proliferate and secrete Th1-like cytokines. This unexpected response of human mDCs to P. falciparum exhibited a transcriptional program distinct from a classical LPS response, pointing to unique P. falciparum-induced activation pathways that may explain the uncharacteristic immune response to malaria.

• 出版日期2017-12-5
• 单位NIH