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Infection and Immunity, February 2009, p. 770-782, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.00994-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Dendritic Cell and NK Cell Reciprocal Cross Talk Promotes Gamma Interferon-Dependent Immunity to Blood-Stage Plasmodium chabaudi AS Infection in Mice {triangledown}

Rebecca Ing1 and Mary M. Stevenson1,2*

Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, McGill University, Montréal, Québec, Canada,1 Centre for Host-Parasite Interactions, Institute of Parasitology, McGill University, Montréal, Québec, Canada2

Received 8 August 2008/ Returned for modification 12 September 2008/ Accepted 12 November 2008

Dendritic cells (DCs) are important accessory cells for promoting NK cell gamma interferon (IFN-{gamma}) production in vitro in response to Plasmodium falciparum-infected red blood cells (iRBC). We investigated the requirements for reciprocal activation of DCs and NK cells leading to Th1-type innate and adaptive immunity to P. chabaudi AS infection. During the first week of infection, the uptake of iRBC by splenic CD11c+ DCs in resistant wild-type (WT) C57BL/6 mice was similar to that in interleukin 15–/– (IL-15–/–) and IL-12p40–/– mice, which differ in the severity of P. chabaudi AS infection. DCs from infected IL-15–/– mice expressed costimulatory molecules, produced IL-12, and promoted IFN-{gamma} secretion by WT NK cells in vitro as efficiently as WT DCs. In contrast, DCs from infected IL-12p40–/– mice exhibited alterations in maturation and cytokine production and were unable to induce NK cell IFN-{gamma} production. Coculture of DCs and NK cells demonstrated that DC-mediated NK cell activation required IL-12 and, to a lesser extent, IL-2, as well as cell-cell contact. In turn, NK cells from infected WT mice enhanced DC maturation, IL-12 production, and priming of CD4+ T-cell proliferation and IFN-{gamma} secretion. Infected WT mice depleted of NK cells, which exhibit increased parasitemia, had impaired DC maturation and DC-induced CD4+ Th1 cell priming. These findings indicate that DC-NK cell reciprocal cross talk is critical for control and rapid resolution of P. chabaudi AS infection and provide in vivo evidence for the importance of this interaction in IFN-{gamma}-dependent immunity to malaria.


* Corresponding author. Mailing address: Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montréal, Québec, H3G 1A4, Canada. Phone: (514) 934-1934, ext. 44507. Fax: (514) 934-8332. E-mail: mary.stevenson{at}mcgill.ca

{triangledown} Published ahead of print on 17 November 2008.

Editor: W. A. Petri, Jr.


Infection and Immunity, February 2009, p. 770-782, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.00994-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.