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Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and BALB/c mice
Joshua G McCaskill1, Kelly D Chason, Xiaoyang Hua
1Department of Medicine, Division of Pulmonary Diseases and Cricital Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7219, USA.
Abstract:
Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium implicated as a putative etiologic agent of sarcoidosis. To characterize the pulmonary immune response to PA, C57BL/6 and BALB/c mice were intraperitoneally sensitized and intratracheally challenged with heat-killed bacteria. C57BL/6 mice challenged with PA developed a cellular immune response characterized by elevations in Th1 cytokines/chemokines, increased numbers of lymphocytes and macrophages in lung lavage fluid, and peribronchovascular granulomatous inflammation composed of T- and B-lymphocytes and epithelioid histiocytes. T-lymphocytes in the lung lavage fluid showed a marked CD4+ cell predominance. In contrast, C57BL/6 mice challenged with Staphylococcus epidermidis (SE), another gram-positive commensal of human skin, and BALB/c mice challenged with PA, showed only a modest induction of Th1 cytokines, less pulmonary inflammation, and no granulomatous changes in the lung. Enhancement of Toll-like receptor expression was seen in PA-exposed C57BL/6 mice within 24 h after exposure, suggesting that induction of innate immunity by PA contributes to the robust, polarized Th1 immune response elicited by this bacterium. These findings suggest that PA-induced pulmonary inflammation may be a useful model for testing the contributions of both bacterial and host factors in the development, maintenance, and resolution of granulomatous inflammation in the lung.
Insights
Propionibacterium acnes (PA) triggers a strong Th1 immune response and granulomatous inflammation in mouse lungs. This suggests PA may be a key factor in sarcoidosis development.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium linked to sarcoidosis.
- Understanding the pulmonary immune response to PA is crucial for sarcoidosis research.
Purpose of the Study:
- To characterize the pulmonary immune response to Propionibacterium acnes (PA) in a mouse model.
- To investigate the role of PA in inducing granulomatous inflammation in the lungs.
Main Methods:
- C57BL/6 and BALB/c mice were sensitized and challenged with heat-killed PA or Staphylococcus epidermidis (SE).
- Pulmonary immune responses, including cytokine/chemokine levels, cell infiltration, and lung histology, were analyzed.
- Toll-like receptor expression was assessed in PA-exposed mice.
Main Results:
- PA challenge in C57BL/6 mice induced a robust Th1 immune response, characterized by elevated Th1 cytokines, increased lymphocytes and macrophages, and granulomatous inflammation.
- A CD4+ T-cell predominance was observed in the lung lavage fluid of PA-challenged C57BL/6 mice.
- SE challenge or PA challenge in BALB/c mice resulted in a modest immune response with minimal inflammation and no granulomas.
- PA exposure enhanced Toll-like receptor expression, suggesting innate immunity activation.
Conclusions:
- PA induces a potent, polarized Th1 immune response and granulomatous inflammation in C57BL/6 mice, unlike SE.
- The findings suggest PA plays a significant role in driving pulmonary inflammation and granuloma formation.
- This PA-induced pulmonary inflammation model is valuable for studying granulomatous inflammation in sarcoidosis and other lung diseases.
