Monocyte-Derived CD11c + Cells Acquire Plasmodium from Hepatocytes to Prime CD8 T Cell Immunity to Liver-Stage Malaria

Abstract

Plasmodium sporozoites inoculated by mosquitoes migrate to the liver and infect hepatocytes prior to release of merozoites that initiate symptomatic blood-stage malaria. Plasmodium parasites are thought to be restricted to hepatocytes throughout this obligate liver stage of development, and how liver-stage-expressed antigens prime productive CD8 T cell responses remains unknown. We found that a subset of liver-infiltrating monocyte-derived CD11c + cells co-expressing F4/80, CD103, CD207, and CSF1R acquired parasites during the liver stage of malaria, but only after initial hepatocyte infection. These CD11c + cells found in the infected liver and liver-draining lymph nodes exhibited transcriptionally and phenotypically enhanced antigen-presentation functions and primed protective CD8 T cell responses against Plasmodium liver-stage-restricted antigens. Our findings highlight a previously unrecognized aspect of Plasmodium biology and uncover the fundamental mechanism by which CD8 T cell responses are primed against liver-stage malaria antigens. There is an urgent need for effective vaccine strategies to protect against malaria. Kurup et al. describe the fundamental mechanisms by which protective CD8 T cell responses are elicited against the liver stage of malaria, possibly helping to refine the rational design of anti-malarial vaccines.