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J Immunol. 2011 Jul 1;187(1):401-11. doi: 10.4049/jimmunol.1002519. Epub 2011 Jun 3.

NK cells promote type 1 T cell immunity through modulating the function of dendritic cells during intracellular bacterial infection.

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  • 1Laboratory for Infection and Immunity, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3.

Abstract

Dendritic cells (DC) play a key role in establishing protective adaptive immunity in intracellular bacterial infections, but the cells influencing DC function in vivo remain unclear. In this study, we investigated the role of NK cells in modulating the function of DC using a murine Chlamydia infection model. We found that the NK cell-depleted mice showed exacerbated disease after respiratory tract Chlamydia muridarum infection, which was correlated with altered T cell cytokine profile. Furthermore, DC from C. muridarum-infected NK-depleted mice (NK(-)DC) exhibited a less mature phenotype compared with that of DC from the infected mice without NK depletion (NK(+)DC). NK(-)DC produced significantly lower levels of both IL-12 and IL-10 than those of NK(+)DC. Moreover, NK(-)DC showed reduced ability to direct primary and established Ag-specific Th1 CD4(+) T cell responses in DC-T coculture systems. More importantly, adoptive transfer of NK(-)DC, in contrast to NK(+)DC, failed to induce type 1 protective immunity in recipients after challenge infection. Finally, NK cells showed strong direct enhancing effect on IL-12 production by DC in an NK-DC coculture system, which was partially reduced by blocking NKG2D receptors signaling and virtually abolished by neutralizing IFN-γ activity. The data demonstrate a critical role of NK cells in modulating DC function in an intracellular bacterial infection.

PMID:
21642541
DOI:
10.4049/jimmunol.1002519
[PubMed - indexed for MEDLINE]
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