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

Author:

Nagamatsu Kanna1,Kuwae Asaomi1,Konaka Tadashi1,Nagai Shigenori23,Yoshida Sei23,Eguchi Masahiro1,Watanabe Mineo1,Mimuro Hitomi4,Koyasu Shigeo235,Abe Akio1

Affiliation:

1. Laboratory of Bacterial Infection and Laboratory of Immunoregulation, Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan

2. Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan

3. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075, Japan

4. Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

5. Research Center for Science Systems, Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo 102-8472, Japan

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 κB p65 (NF-κBp65) but, in contrast, promotes nuclear translocation of NF-κBp50. 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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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