Atypical activation of dendritic cells by <i>Plasmodium falciparum</i>.

Abstract

Dendritic cells (DCs) are activated by pathogens to initiate and shape immune responses. We found that the activation of DCs by <i>Plasmodium falciparum</i>, 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-1β, IL-6, IL-10, TNF). Similar results were obtained with DCs obtained from malaria-naïve 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-α secretion in response to the parasite. Despite the absence of inflammatory cytokine secretion, mDCs incubated with <i>P. falciparum</i>-infected erythrocytes activated antigen-specific naïve CD4⁺ T cells to proliferate and secrete Th1-like cytokines. This unexpected response of human mDCs to <i>P. falciparum</i> exhibited a transcriptional program distinct from a classical LPS response, pointing to unique <i>P. falciparum</i>-induced activation pathways that may explain the uncharacteristic immune response to malaria.