Morgenstern Alexis R, Peterson Liam F, Arnold Kimberly A, Brewer Matthew G
Department of Dermatology, University of Rochester, Rochester, New York, USA.
Department of Pathology & Laboratory Medicine, University of Rochester, Rochester, New York, USA.
mSphere. 2024 Apr 23;9(4):e0068523. doi: 10.1128/msphere.00685-23. Epub 2024 Mar 19.
is a leading cause of skin and soft tissue infections. Colonization by this bacterium is increased in individuals with chronic cutaneous diseases such as atopic dermatitis, psoriasis, and bullous pemphigoid. The greater abundance of on the skin of subjects with atopic dermatitis in particular has been linked to recurrent cutaneous infections. The primary cell type of the epidermal layer of the skin is the keratinocyte, and it is thought that internalized in keratinocytes associates with an increased incidence of skin infections. This study addresses whether keratinocyte differentiation and/or inflammation, two important characteristics altered in cutaneous diseases, influence bacterial internalization. To do this, internalization was measured in immortalized and primary keratinocytes that were differentiated using high Ca-containing media and/or exposed to cytokines characteristic of atopic dermatitis (IL-4 and IL-13) or psoriasis (IL-17A and IL-22) skin. Our results indicate that internalization is uniquely decreased upon keratinocyte differentiation, since this was not observed with another skin-resident bacterium, . Additionally, treatment with IL-4 + IL-13 diminished bacterial internalization. We interpret this decrease as a mechanism of keratinocyte-based bacterial killing since a similar number of bacterial genomes were detected in cytokine-treated cells, but less viable internalized was recovered. Finally, of the receptors reported for binding/internalizing into keratinocytes, expression of the α component of the αβ integrin was in greatest accordance with the number of internalized bacteria in the context of keratinocyte differentiation.IMPORTANCEIndividuals with chronic cutaneous diseases demonstrate heightened susceptibility for severe and recurrent infections from . What drives this altered susceptibility remains poorly understood. Previous publications have detected as deep as the dermal layer of skin in subjects with atopic dermatitis, suggesting that the cutaneous environment of this disease enables deeper bacterial infiltration than occurs in healthy individuals. This observation indicates that has greater opportunity to interact with multiple skin cell types in individuals with chronic inflammatory skin diseases. Identifying the characteristics of the skin that influence bacterial internalization, a common method to establish reservoirs and evade the immune response, is critical for our understanding of pathogenesis. The significance of this research is the novel identification of epidermal characteristics that influence internalization. With this knowledge, methods can be developed to identify patient populations at greater risk for cutaneous infections.
是皮肤和软组织感染的主要原因。在患有慢性皮肤病如特应性皮炎、银屑病和大疱性类天疱疮的个体中，这种细菌的定植会增加。特别是在特应性皮炎患者的皮肤上，该菌数量更多，这与复发性皮肤感染有关。皮肤表皮层的主要细胞类型是角质形成细胞，据认为，角质形成细胞内化该菌与皮肤感染发生率增加有关。本研究探讨了角质形成细胞分化和/或炎症这两个在皮肤病中改变的重要特征是否会影响细菌内化。为此，在永生化和原代角质形成细胞中测量细菌内化情况，这些细胞使用高钙培养基进行分化和/或暴露于特应性皮炎（IL-4和IL-13）或银屑病（IL-17A和IL-22）皮肤特征性的细胞因子中。我们的结果表明，角质形成细胞分化后该菌内化会独特地减少，因为在另一种皮肤常驻细菌中未观察到这种情况。此外，用IL-4 + IL-13处理可减少细菌内化。我们将这种减少解释为角质形成细胞介导的细菌杀伤机制，因为在细胞因子处理的细胞中检测到的细菌基因组数量相似，但回收的活内化菌较少。最后，在报道的用于该菌结合/内化到角质形成细胞的受体中，αβ整合素的α成分的表达与角质形成细胞分化背景下内化细菌的数量最一致。
重要性
患有慢性皮肤病的个体对该菌引起的严重和复发性感染表现出更高的易感性。导致这种易感性改变的原因仍知之甚少。先前的出版物在特应性皮炎患者的皮肤真皮层深处检测到该菌，这表明这种疾病的皮肤环境使得细菌能够比健康个体更深地渗透。这一观察结果表明，在患有慢性炎症性皮肤病的个体中，该菌有更多机会与多种皮肤细胞类型相互作用。确定影响细菌内化的皮肤特征，这是建立菌库和逃避免疫反应的常见方式，对于我们理解该菌的发病机制至关重要。这项研究的意义在于首次确定了影响该菌内化的表皮特征。有了这些知识，就可以开发方法来识别皮肤感染风险更高的患者群体。
