CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes

Sumana Chakravarty, Ian A. Cockburn, Salih Kuk, Michael G. Overstreet, John B. Sacci, Fidel P Zavala

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1035-1041
Number of pages7
JournalNature Medicine
Volume13
Issue number9
DOIs
StatePublished - Sep 2007

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T-cells
Liver
Malaria
Skin
Lymph Nodes
T-Lymphocytes
Immunity
Plasmodium yoelii
Immunization
Sporozoites
Cytoprotection
Plasmodium
Antigen-Presenting Cells
Bites and Stings
Ablation
Culicidae
Dendritic Cells
Hepatocytes
Bone
Vaccination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. / Chakravarty, Sumana; Cockburn, Ian A.; Kuk, Salih; Overstreet, Michael G.; Sacci, John B.; Zavala, Fidel P.

In: Nature Medicine, Vol. 13, No. 9, 09.2007, p. 1035-1041.

Research output: Contribution to journalArticle

Chakravarty, S, Cockburn, IA, Kuk, S, Overstreet, MG, Sacci, JB & Zavala, FP 2007, 'CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes', Nature Medicine, vol. 13, no. 9, pp. 1035-1041. https://doi.org/10.1038/nm1628
Chakravarty, Sumana ; Cockburn, Ian A. ; Kuk, Salih ; Overstreet, Michael G. ; Sacci, John B. ; Zavala, Fidel P. / CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. In: Nature Medicine. 2007 ; Vol. 13, No. 9. pp. 1035-1041.
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