Sarcoidosis is caused by Th1-type immune responses to unknown agents, and is linked to the infectious agent Propionibacterium acnes. Many strains of P. acnes isolated from sarcoid lesions cause intracellular infection and autophagy may contribute to the pathogenesis of sarcoidosis. We examined whether P. acnes induces autophagy.

Propionibacterium acnes is a human skin commensal that resides preferentially within sebaceous follicles and is the only microorganism that has been isolated from sarcoid lesions. We report the complete genome sequence of P. acnes, which was isolated from a Japanese patient with sarcoidosis.

Propionibacterium acnes is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect P. acnes-derived immune complexes in sarcoid lesions.

Sarcoidosis likely results from the exposure of a genetically susceptible subject to an environmental agent, possibly an infectious one. Mycobacterial and propionibacterial organisms are the most commonly implicated potential etiologic agents. Propionibacterium acnes is the only microorganism, however, found in sarcoid lesions by bacterial culture. To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in sarcoid and non-sarcoid tissues using immunohistochemical methods with novel P. acnes-specific monoclonal antibodies that react with cell-membrane-bound lipoteichoic acid (PAB antibody) and ribosome-bound trigger-factor protein (TIG antibody). We examined formalin-fixed and paraffin-embedded samples of lungs and lymph nodes from 196 patients with sarcoidosis, and corresponding control samples from 275 patients with non-sarcoidosis diseases. The samples were mostly from Japanese patients, with 64 lymph node samples from German patients. Immunohistochemistry with PAB antibody revealed small round bodies within sarcoid granulomas in 20/27 (74%) video-assisted thoracic surgery lung samples, 24/50 (48%) transbronchial lung biopsy samples, 71/81 (88%) Japanese lymph node samples, and 34/38 (89%) German lymph node samples. PAB antibody did not react with non-sarcoid granulomas in any of the 45 tuberculosis samples or the 34 samples with sarcoid reaction. In nongranulomatous areas, small round bodies detected by PAB antibody were found in alveolar macrophages of lungs and paracortical macrophages of lymph nodes from many sarcoid and some non-sarcoid patients. Large-spheroidal acid-fast bodies, Hamazaki-Wesenberg bodies, which were found in 50% of sarcoid and 15% of non-sarcoid lymph node samples, reacted with both PAB and TIG antibodies. Electron microscopy revealed that these Hamazaki-Wesenberg bodies had a single bacterial structure and lacked a cell wall with occasional protrusions from the body. The high frequency and specificity of P. acnes, detected by PAB antibody within sarcoid granulomas, indicates that this indigenous bacterium might be the cause of granuloma formation in many sarcoid patients.

Propionibacterium acnes is one of the most commonly implicated etiologic agents of sarcoidosis. We previously reported a complete genome sequence of the C1 strain of P. acnes as a clinical isolate from subcutaneous granulomatous inflammatory lesions in a patient with sarcoidosis. In the present study, we initially searched for genetic profiles specific to the C1 strain by core genome analysis and multiple genome alignment with database sequences from 76 and 9 P. acnes strains, respectively. The analysis revealed that the C1 strain was phylogenetically independent and carried an 18.8-kbp transposon sequence unique to the sarcoid isolate. The unique composite transposon comprised a novel insertion sequence and extrinsic genes from bacteria other than P. acnes. Multilocus sequence typing using 24 sarcoid and 36 non-sarcoid isolates revealed a total of 28 sequence types (STs), including ST26, which was most frequently found without specificity for sarcoid isolates. All 13 ST26 isolates exhibited cell-invasiveness and were confirmed to carry the novel insertion sequence and 4 of the 27 extrinsic CDSs in the transposon, with one exception. ST26 of P. acnes with the composite transposon is the most unique strain detected to date and should be further examined as a causative strain of sarcoidosis.