Rapid pathogen-specific recruitment of immune effector cells in the skin by secreted toxins. Homo sapiens

Swift recruitment of phagocytic leukocytes is critical to prevent infection when bacteria breach through the protective layers of the skin. According to canonical models, this occurs via an indirect process that is initiated by contact of bacteria with resident skin cells and which is independent of the pathogenic potential of the invader. Here, we describe a more rapid mechanism of leukocyte recruitment to the site of intrusion of the important skin pathogen Staphylococcus aureus that is based on direct recognition of specific bacterial toxins, the phenol-soluble modulins (PSMs), by circulating leukocytes. This early recruitment was dependent on the transcription factor EGR1 and significantly contributed to the prevention of infection. Our findings refine the classical notion of the non-specific and resident cell-dependent character of the innate immune response to bacterial infection by demonstrating a pathogen-specific high-alert mechanism involving direct recruitment of immune effector cells by secreted bacterial products. Overall design: time series human PMN and various treatments

当细菌突破皮肤保护层时，快速招募吞噬性白细胞是预防感染的关键环节。根据经典免疫学模型，该招募过程通过间接途径完成：细菌与皮肤常驻细胞接触后启动招募，且此过程与入侵者的致病潜力无关。本研究揭示了一种更为快速的白细胞招募机制：针对重要皮肤致病菌金黄色葡萄球菌（Staphylococcus aureus）的入侵部位，循环白细胞可直接识别其分泌的特定细菌毒素——酚可溶性调节蛋白（phenol-soluble modulins, PSMs），进而启动招募。该早期招募依赖于转录因子EGR1，且对感染预防具有显著贡献。本研究发现了一种由细菌分泌产物直接招募免疫效应细胞的病原体特异性高预警机制，修正了“细菌感染的固有免疫应答具有非特异性且依赖皮肤常驻细胞”的经典认知。实验整体设计：人类多形核白细胞（polymorphonuclear leukocytes, PMN）的时间序列样本及多种处理组。