IFN‐γ production by CD27+ NK cells exacerbates Listeria monocytogenes infection in mice by inhibiting granulocyte mobilization |
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Authors: | Nuno Viegas Lisa Andzinski Ching‐Fang Wu Ronja‐Melinda Komoll Nelson Gekara Kurt E. Dittmar Siegfried Weiss Jadwiga Jablonska |
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Affiliation: | 1. Molecular Immunology, Helmholtz Centre for Infection Research, HZI, , Braunschweig, Germany;2. Department of Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, HZI, , Braunschweig, Germany |
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Abstract: | Natural killer (NK) cells are key components of the immune system involved in several immune reactions, including the clearance of intracellular pathogens. When activated, NK cells rapidly secrete particular cytokines that activate innate immunity and facilitate development of adaptive responses. Conflicting reports on the role of NK cells during infection by Listeria monocytogenes can be found in the literature. Here, we demonstrate that during lethal infection by L. monocytogenes, activation of NK cells via the costimulatory molecule CD27 leads to excessive IFN‐γ production. This impairs innate anti‐bacterial host defenses by inducing downregulation of CXCR2 on granulocytes and consequently inhibiting their recruitment to the sites of infection. The use of antibodies to block CD27 signaling or to deplete IFN‐γ was sufficient to rescue mice from lethal challenge by L. monocytogenes. Our findings contribute to a better understanding of the importance of CD27 signaling in activation of NK cells and should provide new ways of interfering with infections. |
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Keywords: | Granulocytes IFN‐γ Infection Listeria monocytogenes NK cells |
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