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, Rachael J., Evans, Krystal J., Crabb, Brendan S., Schofield, Louis, and Hansen, Diana S. (2013) NK cells and conventional dendritic cells engage in reciprocal activation for the induction of inflammatory responses during Plasmodium berghei ANKA infection. Immunobiology, 218. 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.

Item ID: 35854
Item Type: Article (Research - C1)
ISSN: 1878-3279
Keywords: CD8T cells, dendritic cells, malaria, NK cells, pathogenesis
Funders: Victorian State Government, National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Project Grant 575538
Date Deposited: 31 Oct 2014 02:36
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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