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

IFN‐γ 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‐γ 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‐γ in the lungs during the acute stage of infection. Stimulation of IFN‐γ 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‐γ 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‐γ, which enhances the anti‐bacterial activity of macrophages, but also promotes the differentiation of Th1 cells.