title: Dendritic cell and NK cell reciprocal cross talk promotes gamma interferon-dependent immunity to blood-stage Plasmodium chabaudi AS infection in mice.
abstract: 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.
authors.affiliation: Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montréal, Québec, H3G 1A4, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ing
authors.forename: Mary M
authors.initials: MM
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000502:physiology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D016788:Plasmodium chabaudi / Q000276:immunology*
chemical_list: D016207:Cytokines; D007371:Interferon-gamma