Journal article
Monocyte-Derived CD11c+ Cells Acquire Plasmodium from Hepatocytes to Prime CD8 T Cell Immunity to Liver-Stage Malaria
Cell host & microbe, Vol.25(4), pp.565-577.e6
04/10/2019
DOI: 10.1016/j.chom.2019.02.014
PMCID: PMC6459714
PMID: 30905437
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.
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•Monocyte-derived CD11c+ cells are recruited during the liver stage of malaria•Liver-infiltrating CD11c+ cells acquire Plasmodium, which requires hepatocyte infection•Plasmodium-harboring CD11c+ cells have distinct phenotypes and transcriptomes•These CD11c+ cells prime protective CD8+ T cells in liver-draining lymph nodes
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.
Details
- Title: Subtitle
- Monocyte-Derived CD11c+ Cells Acquire Plasmodium from Hepatocytes to Prime CD8 T Cell Immunity to Liver-Stage Malaria
- Creators
- Samarchith P Kurup - University of IowaScott M Anthony - University of IowaLisa S Hancox - University of IowaRahul Vijay - University of IowaLecia L Pewe - University of IowaSteven J Moioffer - University of IowaRamakrishna Sompallae - University of IowaChris J Janse - Leiden University Medical CenterShahid M Khan - Leiden University Medical CenterJohn T Harty - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cell host & microbe, Vol.25(4), pp.565-577.e6
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.chom.2019.02.014
- PMID
- 30905437
- PMCID
- PMC6459714
- ISSN
- 1931-3128
- eISSN
- 1934-6069
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: AI42767, AI85515, AI100527, T32 5T32HL007
- Language
- English
- Date published
- 04/10/2019
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984183985302771
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