Staphylococcus aureus Biofilm-Mediated Infections: Characterization of the Host Adaptive Immune Response and its Role in Chronic Infection (45.2)

Abstract

Abstract Staphylococcus aureus is a common cause of prosthetic implant infections, which can become chronic due to the ability of S. aureus to grow as a biofilm. Little is known about adaptive immune responses to these infections in vivo. We hypothesized that S. aureus elicits inflammatory Th1/Th17 responses, associated with biofilm formation, instead of protective Th2/Treg responses. A previously developed mouse model of prosthetic implant infection was modified to produce a long term biofilm infection and used to determine chronic infection rates, Treg frequency, and local cytokine levels in B6 and BALB/c mice. Chronic infection levels in STAT6 KO mice (BALB/c background), BALB/c mice receiving anti-CD25 MAb, and B6 mice receiving anti-IL-6 or anti-IL-12 p40 MAb were also assessed. Local S. aureus implant infection was chronic in 100% of B6 mice, whereas BALB/c mice more effectively cleared the infection and demonstrated higher levels of local Th2 cytokines and Tregs. STAT6 KO mice lost the ability to effectively clear an S. aureus implant infection, as did BALB/c mice receiving anti-CD25. In contrast, B6 mice treated with anti-IL-12 p40 were able to more effectively clear the infection. These results indicate that Th2/Treg responses are mechanisms of protection against chronic S. aureus implant infection, as opposed to Th1/Th17 responses, which may play a role in development of chronic implant infection. Our results also suggest that anti-IL-12 p40 MAb may be used therapeutically.