The pro-inflammatory and anti-inflammatory TLR2 responses to Staphylococcus aureus can be uncoupled (P1242)

Abstract

Abstract Microbial detection by pattern recognition receptors (PRRs) is typically associated with a pro-inflammatory cytokine response that primes adaptive immunity. However, some PRRs may also elicit an anti-inflammatory response. Most notably, LPS engagement to Toll-like receptor 4 (TLR4) leads to a PI3K-dependent internalization of TLR4, and the production of Type I interferons and, subsequently, of the anti-inflammatory cytokine IL-10. We have previously reported that peptidoglycan-embedded molecules in the gram-positive bacterium Staphylococcus aureus cell wall, acting on TLR2 on monocytes and macrophages, trigger a PI3K/Akt-dependent IL-10 response that can suppress adaptive T cell immunity. We now report that, unlike the anti-inflammatory TLR4 response, the TLR2-mediated anti-inflammatory IL-10 response is independent of actin-mediated receptor internalization and Type I interferon production. More importantly, the anti-inflammatory response triggered by S. aureus isolates through TLR2 can be uncoupled from the pro-inflammatory response, as they have different kinetics and TLR2 internalization requirements. Our data reveal a novel mechanism of TLR-mediated anti-inflammatory response that may be triggered by selective ligands on the staphylococcal cell wall. Identification of these anti-inflammatory TLR2 ligands may be a first step toward designing novel therapies to treat staphylococcal infections.