Dendritic Cells in Blood-Stage Malaria: Orchestrators of Immune Responses and Pathogenesis

Malaria remains a major global health burden, and immune responses during the blood stage are essential for both parasite control and disease pathogenesis. Conventional dendritic cells (cDCs) occupy a central position at the interface between innate and adaptive immunity, yet their diverse roles during blood-stage malaria remain incompletely understood. This review summarizes current knowledge of cDC biology in malaria, with particular emphasis on findings from murine models. Blood-stage Plasmodium infection alters splenic cDC populations and activates cDCs through parasite-derived and host-derived signals, including glycosylphosphatidylinositols, nucleic acids, hemozoin, and uric acid. Activated cDCs regulate CD4+ T-cell differentiation, including Th1, Th2, Tfh, and Th17 responses, and cDC1-mediated cross-presentation contributes to pathogenic CD8+ T-cell responses in experimental cerebral malaria. cDCs also interact with macrophages, γδ T cells, NK cells, and other innate lymphoid populations, thereby shaping both protective immunity and immunopathology. Important unresolved questions include the roles of cDCs in immunity to gametocytes, placental malaria, repeated malaria exposure, trained immunity, and vaccine responsiveness. Further characterization of cDC subset-specific functions may improve understanding of malaria immunity and identify new strategies for vaccines and immunomodulatory interventions.