Bacterial lipoproteins and TLR2

TLR2 recognizes bacterial lipoproteins, which are expressed by gram-positive and gram-negative bacteria. TLR2 participates in host defenses against bacterial infections. We found that gram-negative bacteria shed commonly expressed bacterial lipoproteins, including peptidoglycan-associated lipoprotein (Pal), into models of sepsis and into human serum. Bacterial lipoproteins activate multiple cell lineages, including leukocytes and non-leukocyte populations, such as endothelial cells and cardiomyocytes. We showed that bacterial TLR2 agonists induce systemic, cardiac and lung inflammation, and cause respiratory dysfunction in mice. We found that TLR2 agonists synergistically induce inflammation with other TLR agonists based on signaling of the TLR agonists via TRIF and MyD88.