Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection.
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.
Mydel
Piotr
P
Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.
Takahashi
Yusuke
Y
Yumoto
Hiromichi
H
Sztukowska
Maryta
M
Kubica
Malgorzata
M
Gibson
Frank C
FC
Kurtz
Donald M
DM
Travis
Jim
J
Collins
L Vincent
LV
Nguyen
Ky-Anh
KA
Genco
Caroline Attardo
CA
Potempa
Jan
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D016866:Bacteroidaceae Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005288:Ferredoxins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D006422:Hemerythrin; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016897:Respiratory Burst / Q000235:genetics / Q000276:immunology*; D012416:Rubredoxins
D000975:Antioxidants; D001426:Bacterial Proteins; D005288:Ferredoxins; D006422:Hemerythrin; D012416:Rubredoxins; C055857:rubrerythrins; D019255:NADPH Oxidases