Investigating how bacteriophages influence the human immune response to Propionibacterium acnes (P3148)

Abstract

Abstract Numerous lines of evidence implicate the Gram-positive skin commensal, Propionibacterium acnes, in the pathogenesis of acne vulgaris, in part by eliciting a host inflammatory response. The emergence of antibiotic resistance in up to 60% of P. acnes isolates, along with the adverse side effects of current treatments has highlighted the need for the development of safer and more effective anti-acne therapeutics. We have investigated the bacteriophages that infect and kill P. acnes and found that they have limited genetic diversity and broad host ranges against clinical isolates, pointing to the potential utility of a phage-based acne treatment. Here, we explored whether these phages, by lysing P. acnes, influence the human immune response to the bacteria. Human monocytes were cultured in the presence of phage-killed or live bacteria, and cytokine responses were measured. We found that monocytes cultured with phage-killed bacteria secrete lower levels of pro-inflammatory cytokines, such as TNFα, IL-1β and IL-12p40, as compared to those infected with live bacteria; phage alone did not stimulate a response. This pattern was also observed when phage and bacteria were added concurrently, that is, during active phage infection, and in all cases, this was consistent across multiple donors. These data suggest that bacteriophage-mediated killing of P. acnes bacteria could help to ameliorate the inflammation associated with acne as a therapeutic modality.