Indigenous pulmonary Propionibacterium acnes primes the host in the development of sarcoid-like pulmonary granulomatosis in mice
Indigenous pulmonary Propionibacterium acnes primes the host in the development of sarcoid-like pulmonary granulomatosis in mice
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DOI：
10.1016/s0002-9440(10)63327-5
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发表时间：
2004-08-01
影响因子：
6
通讯作者：
Matsushima, K
中科院分区：
文献类型：
--
作者：
Nishiwaki, T;Yoneyama, H;Matsushima, K
虽然许多结节病病例是自限性的，可自发缓解，但在少数患者中，不受控制的肺肉芽肿病伴纤维化会产生难以忍受的长期呼吸道症状。个体慢性肺结节病需要替代治疗皮质类固醇治疗，因为其有效性不足。尽管许多研究人员认为感染是该病的触发因素，但候选致病生物诱发这种疾病的机制尚不清楚。我们在此报道，肺外对痤疮丙酸杆菌的致敏，这是迄今为止的候选之一，诱导肺Th-1肉芽肿主要发生在结节病中常见的胸膜下和支气管血管周围区域。这些肉芽肿似乎是由正常肺下呼吸道存在的原生性痤疮（被认为是无菌的）和由循环中涌入的痤疮痤疮敏感的CD4(+) T细胞引起的。重要的是，用抗生素根除本地痤疮假单胞菌可减轻肉芽肿；肺病。这是第一个报告，提出明确的证据，本地肺细菌的贡献，以形成肉芽肿病变在肺。我们建议针对肺中原生性痤疮的治疗可能是治疗肺结节病的一种可能的方法。
Although many cases of sarcoidosis are self-limiting with spontaneous remission, uncontrolled pulmonary granulomatosis with fibrosis produces intolerable longterm respiratory symptoms in a minority of patients. individuals with chronic pulmonary sarcoidosis require an alternative therapy to corticosteroidal treatment because of its insufficient effectiveness. Although many researchers have considered infection as the triggering factor for this disease, the mechanisms by which the candidate causative organisms induce this disorder remain unclear. We report here that extrapulmonary sensitization to Propionibacterium acnes, which is one of the candidates to date, induced pulmonary Th-1 granulomas mainly in die subpleural and peribronchovascular regions often observed in sarcoidosis. These granulomas appear to be caused by indigenous P. acnes pre-existing in the lower respiratory tract of the normal lung, which is believed to be germ-free, and by an influx of P. acnes-sensitized CD4(+) T cells from the circulation. Importantly, the eradication of indigenous P. acnes with antibiotics alleviated the granulomatous; lung disease. This is the first report to present clear evidence of the contribution of an indigenous pulmonary bacterium to the formation of granulomatous lesions in the lung. We propose that treatment targeting indigenous P. acnes in the lung may be a possible remedy for pulmonary sarcoidosis.