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

鉴定参与先天免疫识别金黄色葡萄球菌的受体，这是人类发病和死亡的主要原因，对于开发治疗由抗生素耐药菌株引起的感染的替代策略至关重要。在目前的研究中，我们使用涉及遗传缺陷小鼠的感染模型来检查内体 TLRs 在抗葡萄球菌宿主防御中的作用，它感知原核型核酸的存在。TLR7、9 或 13 中的单一缺陷导致宿主防御轻度或无下降。然而，TLR7、9 和 13 同时缺失导致对皮肤和全身性金黄色葡萄球菌的易感性显着增加感染伴随着促炎趋化因子和细胞因子的产生减少，中性粒细胞向感染部位募集，以及活性氧的产生减少。这种表型比缺乏 TLR2 的小鼠严重得多，TLR2 能感知葡萄球菌脂蛋白的存在。值得注意的是，TLR7、9 和 13 的联合缺失导致 IL-12 p70 和 IFN-β 对巨噬细胞中葡萄球菌刺激的反应完全消除。总之，我们的数据突出了高度集成的内体检测系统的存在，其中 TLR7、9 和 13 合作检测葡萄球菌核酸的存在。我们证明这些受体的联合缺失不能通过细胞表面相关的 TLRs，如 TLR2 或细胞质受体来补偿。金黄色葡萄球菌感染。