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(American Journal of Pathology. 2004;165:631-639.)
© 2004 American Society for Investigative Pathology

Indigenous Pulmonary Propionibacterium acnes Primes the Host in the Development of Sarcoid-Like Pulmonary Granulomatosis in Mice

Tetsu Nishiwaki*{dagger}, Hiroyuki Yoneyama*, Yoshinobu Eishi{ddagger}, Naoki Matsuo*{dagger}, Koichiro Tatsumi{dagger}, Hiroshi Kimura§, Takayuki Kuriyama{dagger} and Kouji Matsushima*

From the Department of Molecular Preventive Medicine and Solution Oriented Research for Science and Technology,* The University of Tokyo School of Medicine, Tokyo; the Department of Respirology,{dagger} Chiba University School of Medicine, Chiba; the Department of Human Pathology,{ddagger} School of Medicine, Tokyo Medical and Dental University, Tokyo; and the Second Department of Internal Medicine,§ Nara Medical University of Medicine, Nara, Japan

Although many cases of sarcoidosis are self-limiting with spontaneous remission, uncontrolled pulmonary granulomatosis with fibrosis produces intolerable long-term 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 the 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.




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