α-溶血素介导的内皮损伤是金黄色葡萄球菌诱导的硬皮病发展的原因之一。

IF 2.9 3区 医学 Q3 IMMUNOLOGY
Infection and Immunity Pub Date : 2024-08-13 Epub Date: 2024-07-02 DOI:10.1128/iai.00133-24
Ching Yang, Frank H Robledo-Avila, Santiago Partida-Sanchez, Christopher P Montgomery
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引用次数: 0

摘要

金黄色葡萄球菌α溶血素(Hla)是一种孔隙形成毒素,对皮肤和软组织感染的发病机制至关重要,在小鼠模型中会导致皮肤坏死(坏死组织)的病理标志性病变。为了确定金黄色葡萄球菌皮肤感染时发生坏死的机制,给小鼠注射对照血清、Hla中和抗血清或Hla受体抑制剂[A-二整合素和金属蛋白酶10(ADAM10)抑制剂],然后用金黄色葡萄球菌进行皮下感染,并用免疫组化和免疫荧光对病变进行评估。Hla 在感染后 6 小时诱导血管内皮细胞凋亡,随后在感染后 24 小时诱导角质形成细胞凋亡。血管内皮(VE)-cadherin表达的丧失先于上皮-cadherin表达的丧失。在血管损伤后24小时,Hla还诱导角质形成细胞缺氧。用Hla中和抗体或ADAM10抑制剂治疗可减轻VE-cadherin的早期裂解、皮肤缺氧和坏死。这些研究结果表明,Hla介导的血管损伤和皮肤缺氧是金黄色葡萄球菌诱导的硬皮病的发病机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
α-Hemolysin-mediated endothelial injury contributes to the development of Staphylococcus aureus-induced dermonecrosis.

Staphylococcus aureus α-hemolysin (Hla) is a pore-forming toxin critical for the pathogenesis of skin and soft tissue infections, which causes the pathognomonic lesion of cutaneous necrosis (dermonecrosis) in mouse models. To determine the mechanism by which dermonecrosis develops during S. aureus skin infection, mice were given control serum, Hla-neutralizing antiserum, or an inhibitor of Hla receptor [A-disintegrin and metalloprotease 10 (ADAM10) inhibitor] followed by subcutaneous infection by S. aureus, and the lesions were evaluated using immunohistochemistry and immunofluorescence. Hla induced apoptosis in the vascular endothelium at 6 hours post-infection (hpi), followed by apoptosis in keratinocytes at 24 hpi. The loss of vascular endothelial (VE)-cadherin expression preceded the loss of epithelial-cadherin expression. Hla also induced hypoxia in the keratinocytes at 24 hpi following vascular injury. Treatment with Hla-neutralizing antibody or ADAM10 inhibitor attenuated early cleavage of VE-cadherin, cutaneous hypoxia, and dermonecrosis. These findings suggest that Hla-mediated vascular injury with cutaneous hypoxia underlies the pathogenesis of S. aureus-induced dermonecrosis.

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来源期刊
Infection and Immunity
Infection and Immunity 医学-传染病学
CiteScore
6.00
自引率
6.50%
发文量
268
审稿时长
3 months
期刊介绍: Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.
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