Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
University of Maryland School of Medicine, Baltimore, MD, USA.
Nat Microbiol. 2022 Jan;7(1):62-72. doi: 10.1038/s41564-021-01012-9. Epub 2021 Dec 6.
Swift recruitment of phagocytic leucocytes is critical in preventing 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 leucocyte 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 leucocytes. We used a combination of intravital imaging, ear infection and skin abscess models, and in vitro gene expression studies to demonstrate that this early recruitment was dependent on the transcription factor EGR1 and 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.
当细菌穿透皮肤的保护层时，迅速招募吞噬白细胞对于预防感染至关重要。根据规范模型，这是通过一个间接过程发生的，该过程由细菌与常驻皮肤细胞的接触引发，并且与入侵者的致病潜力无关。在这里，我们描述了一种更快速的白细胞募集到重要皮肤病原体金黄色葡萄球菌入侵部位的机制，该机制基于循环白细胞对特定细菌毒素、酚可溶性调节蛋白（PSM）的直接识别。我们使用体内成像、耳部感染和皮肤脓肿模型以及体外基因表达研究来证明这种早期招募依赖于转录因子 EGR1，并有助于预防感染。我们的发现通过证明涉及由分泌细菌产物直接招募免疫效应细胞的病原体特异性高警报机制，细化了对细菌感染的固有免疫反应的非特异性和常驻细胞依赖性特征的经典概念。
