Depletion of NK cells results in disseminating lethal infection with Bordetella pertussis associated with a reduction of antigen-specific Th1 and enhancement of Th2, but not Tr1 cells.

Abstract:

:IFN-gamma plays a critical role in protection against Bordetella pertussis, but Th1 cells are only detectable after the infection has started to resolve, suggesting a protective role for innate IFN-gamma early in infection. Here, we demonstrate significant recruitment of NK cells and NKT cells into the lungs following respiratory challenge with B. pertussis. Furthermore, NK cells are the primary source of IFN-gamma in the lungs during the acute stage of infection. Stimulation of IFN-gamma production by NK cells was indirect through B. pertussis-activated IL-12 or IL-23 production by dendritic cells. Depletion of NK cells with anti-asialo ganglio-N-tetraosylceramide antibody resulted in a lethal infection, with enhancement of bacterial load in the lungs and dissemination of the bacteria to the liver via the blood. NK cell-depleted mice had significantly reduced B. pertussis-specific IFN-gamma and enhanced IgG1 and IL-5, but not IL-10 production, suggesting that regulatory T cells are induced simultaneously with Th1 cells, but the absence of NK cells resulted in enhancement of Th2-type responses. These findings suggest that NK cells confer resistance to B. pertussis by activating IL-12-mediated production of IFN-gamma, which enhances the anti-bacterial activity of macrophages, but also promotes the differentiation of Th1 cells.

journal_name

Eur J Immunol

authors

Byrne P,McGuirk P,Todryk S,Mills KH

doi

10.1002/eji.200425092

keywords:

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

2579-88

issue

9

eissn

0014-2980

issn

1521-4141

journal_volume

34

pub_type

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