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

Research output: Contribution to journalArticleResearchpeer-review

25 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

Cite this

Ryg-Cornejo, Victoria ; Nie, Catherine Q ; Bernard, Nicholas J. ; Lundie, Rachel J. ; Evans, Krystal J ; Crabb, Brendan S. ; Schofield, Louis D ; Hansen, Diana S. / NK cells and conventional dendritic cells engage in reciprocal activation for the induction of inflammatory responses during Plasmodium berghei ANKA infection. In: Immunobiology. 2013 ; Vol. 218, No. 2. pp. 263-271.
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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.",
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NK cells and conventional dendritic cells engage in reciprocal activation for the induction of inflammatory responses during Plasmodium berghei ANKA infection. / Ryg-Cornejo, Victoria; Nie, Catherine Q; Bernard, Nicholas J.; Lundie, Rachel J.; Evans, Krystal J; Crabb, Brendan S.; Schofield, Louis D; Hansen, Diana S.

In: Immunobiology, Vol. 218, No. 2, 02.2013, p. 263-271.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Ryg-Cornejo, Victoria

AU - Nie, Catherine Q

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AU - Evans, Krystal J

AU - Crabb, Brendan S.

AU - Schofield, Louis D

AU - Hansen, Diana S.

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