Article abstract
Nature Medicine 13, 1035 - 1041 (2007)
Published online: 19 August 2007 | doi:10.1038/nm1628
CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes
Sumana Chakravarty1, Ian A Cockburn1, Salih Kuk1, Michael G Overstreet1, John B Sacci2 & Fidel Zavala1
Abstract
The success of immunization with irradiated sporozoites is unparalleled among the current vaccination approaches against malaria, but its mechanistic underpinnings have yet to be fully elucidated. Using a model mimicking natural infection by Plasmodium yoelii, we delineated early events governing the development of protective CD8+ T-cell responses to the circumsporozoite protein. We demonstrate that dendritic cells in cutaneous lymph nodes prime the first cohort of CD8+ T cells after an infectious mosquito bite. Ablation of these lymphoid sites greatly impairs subsequent development of protective immunity. Activated CD8+ T cells then travel to systemic sites, including the liver, in a sphingosine-1-phosphate (S1P)-dependent fashion. These effector cells, however, no longer require bone marrow–derived antigen-presenting cells for protection; instead, they recognize antigen on parenchymal cells—presumably parasitized hepatocytes. Therefore, we report an unexpected dichotomy in the tissue restriction of host responses during the development and execution of protective immunity to Plasmodium.
- Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, Maryland 21205, USA.
- Department of Microbiology and Immunology, University of Maryland School of Medicine, 660 West Redwood St., Baltimore, Maryland 21201, USA.
Correspondence to: Fidel Zavala1 e-mail: fzavala@jhsph.edu
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