The outer membranes of Gram-negative bacteria and mitochondria contain proteins with a distinct β-barrel tertiary structure that could function as a molecular pattern recognized by the innate immune system. Here, we report that purified outer membrane proteins (OMPs) from different bacterial and mitochondrial sources triggered the induction of autophagy-related endosomal acidification, LC3B lipidation, and p62 degradation. Furthermore, OMPs reduced the phosphorylation and therefore activation of the multiprotein complex mTORC2 and its substrate Akt in macrophages and epithelial cells. The cell surface receptor SlamF8 and the DNA-protein kinase subunit XRCC6 were required for these OMP-specific responses in macrophages and epithelial cells, respectively. The addition of OMPs to mouse bone marrow–derived macrophages infected with Salmonella Typhimurium facilitated bacterial clearance. These data identify a specific cellular response mediated by bacterial and mitochondrial OMPs that can alter inflammatory responses and influence the killing of pathogens.

革兰氏阴性细菌和线粒体的外膜包含具有独特的β-桶三级结构的蛋白质，这些蛋白质可以用作先天免疫系统识别的分子模式。在这里，我们报告从不同的细菌和线粒体来源纯化的外膜蛋白（OMPs）触发了自噬相关的内体酸化，LC3B脂化和p62降解的诱导。此外，OMP减少了巨噬细胞和上皮细胞中磷酸化，从而降低了多蛋白复合物mTORC2及其底物Akt的活化。细胞表面受体SlamF8和DNA蛋白激酶亚基XRCC6分别是巨噬细胞和上皮细胞中这些OMP特异性反应所必需的。在感染了小鼠骨髓的巨噬细胞中添加了OMPs鼠伤寒沙门氏菌有助于细菌清除。这些数据确定了由细菌和线粒体OMP介导的特定细胞反应，可以改变炎症反应并影响病原体的杀灭。