NK cells and conventional dendritic cells engage in reciprocal activation for the induction of inflammatory responses during Plasmodium berghei ANKA infection

Victoria Ryg-Cornejo, Catherine Q Nie, Nicholas J. Bernard, Rachel J. Lundie, Krystal J Evans, Brendan S. Crabb, Louis D Schofield, Diana S. Hansen

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26 Citations (Scopus)

Abstract

Cerebral malaria (CM) is the most severe syndrome associated with Plasmodium falciparum infections. Experimental evidence suggests that disease results from the sequestration of parasitized-red blood cells (pRBCs) together with inflammatory leukocytes within brain capillaries. We have previously shown that NK cells stimulate migration of CXCR3+ T cells to the brain of Plasmodium berghei ANKA-infected mice. Here we investigated whether interactions between NK cells and dendritic cells (DCs) are required for the induction of T cell responses involved in disease. For that, NK cell-depleted and control mice were infected with transgenic parasites expressing model T cell epitopes. T cells from TCR transgenic mice specific for those epitopes were adoptively transferred and proliferation was determined. NK cell depletion significantly reduced CD8+ but not CD4+ DC-mediated T cell priming. Lack of NK cells did not compromise CD8+ T cell responses in IL-12-/- mice, suggesting that NK cells stimulate IL-12 output by DCs required for optimal T cell priming. The contribution of DCs to NK cell function was also investigated. DC depletion and genetic deletion of IL-12 dramatically reduced NK cell-mediated IFN-γ responses to malaria. Thus NK cells and DCs engage in reciprocal activation for the induction of inflammatory responses involved in severe malaria.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalImmunobiology
Volume218
Issue number2
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Keywords

  • CD8 T cells
  • Dendritic cells
  • Malaria
  • NK cells
  • Pathogenesis

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