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Sarcoidosis is a chronic granulomatous disorder of unknown aetiology. This study reports the induction in mice of pulmonary granulomas, similar to those in sarcoidosis, by indigenous Propionibacterium acnes residing in the lower respiratory tract. This was associated with an influx of P acnes sensitised CD4+ T lymphocytes from the circulation and, moreover, eradication of P acnes with antibiotics led to resolution of the granulomas.
Immunostaining and reverse-transcriptase polymerase chain reaction were used to demonstrate P acnes antigen in the lungs and lymph nodes of the mice. Furthermore, lymphocytes from these animals proliferated specifically to P acnes antigen, suggesting prior priming. In a subsequent experiment mice were immunised with P acnes antigen and P acnes sensitised CD4+ T cells were isolated from the inguinal nodes. These T cells were then injected into normal mice and the lungs and liver showed granulomatous changes when examined histologically 2 weeks later. Repeated immunisation with P acnes produced granulomas in the liver, lung and spleen with CD4+ cells expressing interferon-γ but not interleukin-4 (suggesting a Th1 type response), along with increases in the serum calcium and angiotensin-converting enzyme concentrations. Finally, bronchoalveolar lavage performed after immunisation showed increased numbers of both total and CD4+ cells, and the above responses were alleviated by prior intratracheal administration of antibiotics.
This study proposes that the immune response against indigenous P acnes may play a role in the pathogenesis of sarcoidosis, and that antibiotics directed against P acnes may be a potentially effective treatment in this disease.
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