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The Journal of Experimental Medicine

Year: 2010  |  Volume: 206  |  Issue: 13  |  Page No.: 3073 - 3088

Bordetella evades the host immune system by inducing IL-10 through a type III effector, BopN

K Nagamatsu, A Kuwae, T Konaka, S Nagai, S Yoshida, M Eguchi, M Watanabe, H Mimuro, S Koyasu and A. Abe

Abstract

The inflammatory response is one of several host alert mechanisms that recruit neutrophils from the circulation to the area of infection. We demonstrate that Bordetella, a bacterial pathogen, exploits an antiinflammatory cytokine, interleukin-10 (IL-10), to evade the host immune system. We identified a Bordetella effector, BopN, that is translocated into the host cell via the type III secretion system, where it induces enhanced production of IL-10. Interestingly, the BopN effector translocates itself into the nucleus and is involved in the down-regulation of mitogen-activated protein kinases. Using pharmacological blockade, we demonstrated that BopN-induced IL-10 production is mediated, at least in part, by its ability to block the extracellular signal-regulated kinase pathway. We also showed that BopN blocks nuclear translocation of nuclear factor B p65 (NF-Bp65) but, in contrast, promotes nuclear translocation of NF-Bp50. A BopN-deficient strain was unable to induce IL-10 production in mice, resulting in the elimination of bacteria via neutrophil infiltration into the pulmonary alveoli. Furthermore, IL-10–deficient mice effectively eliminated wild-type as well as BopN mutant bacteria. Thus, Bordetella exploits BopN as a stealth strategy to shut off the host inflammatory reaction. These results explain the ability of Bordetella species to avoid induction of the inflammatory response.

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