Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection.
Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection.
复制标题
牙龈卟啉单胞菌感染过程中宿主氧化免疫反应及细菌抗氧化红素氧还蛋白的作用。
DOI：
10.1371/journal.ppat.0020076
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发表时间：
2006-07
期刊：
影响因子：
6.7
通讯作者：
Potempa J
中科院分区：
文献类型：
--
作者：
Mydel P;Takahashi Y;Yumoto H;Sztukowska M;Kubica M;Gibson FC 3rd;Kurtz DM Jr;Travis J;Collins LV;Nguyen KA;Genco CA;Potempa J
中性粒细胞对微生物的有效清除需要白细胞分泌颗粒内活性氧和杀微生物成分的协同作用。赤藓红蛋白（Rbr）是一种非血红素铁蛋白，可保护许多空气敏感性细菌免受氧化应激。使用氧化爆发敲除（NADPH氧化酶无效）小鼠和rbr基因敲除细菌菌株，我们研究了宿主的吞噬细胞氧化爆发和厌氧牙周病原体牙龈卟啉单胞菌的氧化应激反应之间的相互作用。Rbr确保了牙龈卟啉单胞菌在具有完全功能的氧化爆发反应的小鼠中的增殖，但在NADPH氧化酶缺失的小鼠中则不然。此外，Rbr提供的体内保护与体外分离的中性粒细胞的氧化爆发反应无关。虽然吞噬细胞衍生的氧化爆发反应对牙龈卟啉单胞菌感染基本无效，但对Rbr阳性微生物的相应氧化反应通过中性粒细胞的有效动员和全身活化而导致宿主诱导的病理学。看来Rbr还提供了针对活性氮物质的保护，从而确保牙龈卟啉单胞菌在感染宿主中的存活。牙龈卟啉单胞菌中rbr基因的存在也导致感染后更大的口腔骨丢失。总的来说，这些结果表明，宿主氧化爆发通过加剧局部和全身炎症而矛盾地增强牙龈卟啉单胞菌的存活，从而导致与感染相关的发病率和死亡率。中性粒细胞的生理作用是寻找并消灭入侵的微生物。专职吞噬细胞吞噬（吞噬）这些生物体，并使用杀菌肽，酶，有毒活性氧和活性氮的中性粒细胞和巨噬细胞产生的物种杀死他们。不幸的是，在氧化爆发反应中释放的活性氧物质可引起相当大的附带损害，并直接导致感染相关的组织损伤，特别是如果入侵者受到保护，不被中性粒细胞杀死。作者研究了牙龈卟啉单胞菌的发病机制，牙龈卟啉单胞菌是一种厌氧细菌，可引起人类牙周病，并通过细胞质蛋白红红蛋白保护其免受氧化应激。我们发现牙龈卟啉单胞菌不仅对活性氧有抵抗力，而且在小鼠中，赤藓红蛋白可以保护细菌免受活性氮的侵害。这些特征允许牙龈卟啉单胞菌在具有完全功能性氧化爆发反应的动物中增殖。此外，我们证明了中性粒细胞的氧化爆发反应，而不是消除细菌，通过破坏宿主组织和促进病原体的生长和全身传播来加剧疾病。总的来说，这项研究提供了重要的信息，氧依赖性杀伤机制如何在厌氧感染和红菊酯在保护免受病原性厌氧生物体的作用，同时强调限制宿主介导的组织损伤的重要性引起的炎症性疾病的细菌。
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. The physiological role of neutrophils is to seek out and destroy invading microbes. Professional phagocytes engulf (phagocytose) these organisms and kill them using bactericidal peptides, enzymes, toxic reactive oxygen species, and reactive nitrogen species produced by neutrophils and macrophages. Unfortunately, the reactive oxygen species unleashed in an oxidative burst response can cause considerable collateral damage and are directly responsible for infection-associated tissues injuries, especially if the invaders are protected against killing by neutrophils. The authors investigated the pathogenesis of Porphyromonas gingivalis, an anaerobic bacterium that is responsible for human periodontal disease and is protected against oxidative stress by the cytoplasmic protein rubrerythrin. We show that P. gingivalis is not only resistant to reactive oxygen species, but that in mice, rubrerythrin shields the bacterium against reactive nitrogen species. These features allow P. gingivalis to proliferate in animals that possess a fully functional oxidative burst response. Furthermore, we demonstrate that the neutrophil oxidative burst response, rather than eliminating the bacteria, exacerbates disease by damaging host tissues and facilitating growth and systemic dissemination of the pathogen. Collectively, this study provides important information on how oxygen-dependent killing mechanisms operate during anaerobic infection and on the role of rubrerythrin in protecting against a pathogenic anaerobic organism, while emphasizing the importance of limiting host-mediated tissue injury in inflammatory diseases caused by bacteria.
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影响因子：
64.8
作者：
Ahluwalia, J;Tinker, A;Clapp, LH;Duchen, MR;Abramov, AY;Pope, S;Nobles, M;Segal, AW
通讯作者：
Segal, AW
影响因子：
4.3
作者：
COHEN, MS;LEONG, PA;SIMPSON, DM
通讯作者：
SIMPSON, DM
影响因子：
3
作者：
BAKER, PJ;EVANS, RT;ROOPENIAN, DC
通讯作者：
ROOPENIAN, DC
影响因子：
3.1
作者：
Gibson, FC;Genco, CA
通讯作者：
Genco, CA
DOI：
10.1006/bbrc.1999.1075
发表时间：
1999-08-11
影响因子：
3.1
作者：
Banbula, A;Bugno, M;Potempa, J
通讯作者：
Potempa, J