Roles of the Host Oxidative Immune Response and Bacterial Antioxidant Rubrerythrin during Porphyromonas gingivalis Infection

PLoS Pathogens

Jim Travis¹  Jan Potempa¹  Caroline Attardo Genco²  Frank C Gibson III³  Ky-Anh Nguyen⁴  Malgorzata Kubica⁴  Yusuke Takahashi⁴  Hiromichi Yumoto⁴  Piotr Mydel⁵  L. Vincent Collins⁵  Donald M Kurtz Jr.⁵  Maryta Sztukowska⁶ 

[1] Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America;Department of Chemistry and Center for Metalloenzyme Studies, University of Georgia, Athens, Georgia, United States of America;Department of Conservative Dentistry, The University of Tokushima, School of Dentistry, Tokushima, Japan;Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America;Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland;Department of Oral Microbiology, Kanagawa Dental College, Yokosuka, Kanagawa, Japan

关键词: Neutrophils;    Anaerobic bacteria;    Respiratory burst;    Mouse models;    Blood;    Bacterial pathogens;    Macrophages;    Inflammation;   

DOI  :  10.1371/journal.ppat.0020076

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The efficient clearance of microbes by neutrophils requires the concerted action of reactive oxygen species and microbicidal components within leukocyte secretory granules. Rubrerythrin (Rbr) is a nonheme iron protein that protects many air-sensitive bacteria against oxidative stress. Using oxidative burst-knockout (NADPH oxidase–null) mice and an rbr gene knockout bacterial strain, we investigated the interplay between the phagocytic oxidative burst of the host and the oxidative stress response of the anaerobic periodontal pathogen Porphyromonas gingivalis. Rbr ensured the proliferation of P. gingivalis in mice that possessed a fully functional oxidative burst response, but not in NADPH oxidase–null mice. Furthermore, the in vivo protection afforded by Rbr was not associated with the oxidative burst responses of isolated neutrophils in vitro. Although the phagocyte-derived oxidative burst response was largely ineffective against P. gingivalis infection, the corresponding oxidative response to the Rbr-positive microbe contributed to host-induced pathology via potent mobilization and systemic activation of neutrophils. It appeared that Rbr also provided protection against reactive nitrogen species, thereby ensuring the survival of P. gingivalis in the infected host. The presence of the rbr gene in P. gingivalis also led to greater oral bone loss upon infection. Collectively, these results indicate that the host oxidative burst paradoxically enhances the survival of P. gingivalis by exacerbating local and systemic inflammation, thereby contributing to the morbidity and mortality associated with infection.

【 授权许可】

CC BY