Regulation of granuloma formation via Myd88 and Nox2 in a model of pulmonary sarcoidosis (MPF5P.741)

• Published in: The Journal of immunology (1950) Vol. 194; no. 1_Supplement; pp. 137 - 137.4
• Main Authors: Werner, Jessica, Escolero, Sylvia, Hewitt, Jeff, Mak, Tim, Eishi, Yoshinobu, Núñez, Gabriel
• Format: Journal Article
• Language: English
• Published: 01-05-2015
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.194.Supp.137.4

Sarcoidosis is characterized by non-caseating granulomas with an unknown etiology that present primarily in the lung. Propionibacterium acnes, an immunogenic commensal skin bacterium involved in acne vulgaris, has been implicated as a causative agent of sarcoidosis because it has been both detected and cultured from granuloma lesions and lymph nodes of sarcoidosis patients. Here we demonstrate that a strain of P.acnes isolated from a sarcoidosis patient and instilled intratracheally into wild type mice can generate pulmonary granulomas. When mice deficient in the innate immunity adapter protein Myd88 are instilled with P.acnes the number and size of granulomas are increased compared to wild type. Additionally there was an increase in granuloma number and size after instillation with P.acnes in mice deficient in Nox2, a critical component of the phagocyte NAPDH that generates reactive oxygen species for microbial killing within the phagosome. Furthermore mice without Myd88 or Nox2 displayed defective killing of P.acnes in the lung, and wild type mice that were given heat-killed P.acnes produce significantly less granulomas then when given viable P.acnes, suggesting that bacterial killing and/or clearance plays a critical role in the development of pulmonary granulomas. In conclusion viable P.acnes can be used to generate a mouse model of pulmonary sarcoidosis, and Myd88 and Nox2 appear to play a key role in the development of these granulomas.