Propionibacterium acnes induces acute TNFα-mediated apoptosis of hepatocytes followed by inflammatory T-cell-mediated granulomatous hepatitis in mice

The CD3+/TCR alpha beta+ T-cell-mediated hepatic inflammation induced by Propionibacterium acnes could be divided into an acute and a chronic phase. The acute phase occurred within 72 h after injection and displayed hepatic apoptosis. Anti-TNF alpha antibody inhibited both the P. acnes-induced hepatic apoptosis and lymphocyte infiltration seen in this phase, indicating the involvement of this cytokine, Thereafter, a chronic phase was manifested from days 7 to 44 after injection. it was characterized as granulomatous inflammation admired with apoptosis of infiltrating lymphocytes and some hepatocytes. Immunohistochemical staining showed that the infiltrating lymphocytes displayed TNF alpha, TNF type I receptor and a variety of cytokines including IL-1 beta, IL-4, IL-6, IL-10, IFN gamma or IL-12. Interestingly, in naive mice, the arteries in the liver constitutively expressed IFN gamma. Its expression appeared to be substantially increased at 48 h, decreased at 72 h, and increased again on day 14 after P. acnes injection. Furthermore, Fas or Fast was only detected on the lymphocytes within the granuloma, We conclude that P. acnes can induce a TNF alpha-mediated acute hepatic apoptosis which subsequently progress to a T-cell-mediated granulomatous hepatitis with increased expression of multiple cytokines and Fas/FasL.