title: Bordetella evades the host immune system by inducing IL-10 through a type III effector, BopN.
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 kappaB p65 (NF-kappaBp65) but, in contrast, promotes nuclear translocation of NF-kappaBp50. 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.
authors.affiliation: Laboratory of Bacterial Infection, Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Kanna
authors.initials: K
authors.lastname: Nagamatsu
authors.forename: Asaomi
authors.initials: A
authors.lastname: Kuwae
authors.forename: Tadashi
authors.initials: T
authors.lastname: Konaka
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nagai
authors.forename: Sei
authors.initials: S
authors.lastname: Yoshida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Eguchi
authors.forename: Mineo
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hitomi
authors.initials: H
authors.lastname: Mimuro
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
authors.forename: Akio
authors.initials: A
authors.lastname: Abe
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D001884:Bordetella / Q000276:immunology* / Q000472:pathogenicity; D039521:CD11c Antigen / Q000502:physiology; D057131:Immune Evasion; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D014132:Trachea / Q000382:microbiology; D037521:Virulence Factors / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D039521:CD11c Antigen; D016328:NF-kappa B; D012333:RNA, Messenger; D037521:Virulence Factors; D016753:Interleukin-10