Role of Endosomal TLRs in <i>Staphylococcus aureus</i> Infection

Abstract Identification of the receptors involved in innate immune recognition Staphylococcus aureus, a major cause morbidity and mortality humans, is essential to develop alternative strategies treat infections caused by antibiotic-resistant strains. In current study, we examine role endosomal TLRs, which sense presence prokaryotic-type nucleic acids, anti-staphylococcal host defenses using infection models involving genetically defective mice. Single deficiencies TLR7, 9, or 13 resulted mild no decrease defenses. However, simultaneous absence markedly increased susceptibility cutaneous systemic S. aureus concomitantly with decreased production proinflammatory chemokines cytokines, neutrophil recruitment sites, reduced reactive oxygen species. This phenotype was significantly more severe than that mice lacking TLR2, senses staphylococcal lipoproteins. Notably, combined complete abrogation IL-12 p70 IFN-β responses stimulation macrophages. Taken together, our data highlight highly integrated detection system, whereby cooperate sensing acids. We demonstrate these cannot be compensated for cell surface-associated such as cytosolic receptors. These may useful devise aimed at stimulating infections.