Lipoteichoic acid is able to inhibit leukocyte recruitment in vivo

Toll‐like receptors (TLR) are sentinel receptors of the immune system that alert the host to pathogen infiltration and initiate an inflammatory response. Contrary to this paradigm we have shown that the TLR2 ligand, lipoteichoic acid (LTA), isolated from Staphylococcus aureus, is able to actively inhibit acute leukocyte recruitment in vivo. We have employed intravital microscopy of the murine cremaster muscle to monitor leukocyte recruitment into tissue following the induction of acute inflammation. Using this method we have shown that LTA is able to inhibit leukocyte recruitment induced by the TLR4‐ligand, lipopolysaccharide, the TLR2‐ligand, Pam3CSK4, as well as the cytokine, TNFalpha, and the chemokine, MIP2. LTA is unique in this capacity among the TLR2 ligands that we have tested, including; LTA, Pam3CSK4, S‐ and R‐FSL1. Not only do these other TLR2‐ligands not inhibit leukocyte recruitment but they actively induce significant leukocyte recruitment into the tissue. While we were able to demonstrate that the inhibitory capacity of LTA was dependent on TLR2, we have found that the classic adaptor proteins that are associated with TLRs, MyD88 and TRIF, are not required to send this inhibitory signal. Therefore we have identified a physiologically relevant, TLR2‐dependent, anti‐inflammatory pathway that is independent of known TLR signaling cascades.