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表皮社区获得性金黄色葡萄球菌皮肤感染模型。

Epicutaneous model of community-acquired Staphylococcus aureus skin infections.

机构信息

Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, USA.

出版信息

Infect Immun. 2013 Apr;81(4):1306-15. doi: 10.1128/IAI.01304-12. Epub 2013 Feb 4.

Abstract

Staphylococcus aureus is one of the most common etiological agents of community-acquired skin and soft tissue infection (SSTI). Although the majority of S. aureus community-acquired SSTIs are uncomplicated and self-clearing in nature, some percentage of these cases progress into life-threatening invasive infections. Current animal models of S. aureus SSTI suffer from two drawbacks: these models are a better representation of hospital-acquired SSTI than community-acquired SSTI, and they involve methods that are difficult to replicate. For these reasons, we sought to develop a murine model of community-acquired methicillin-resistant S. aureus SSTI (CA-MRSA SSTI) that can be consistently reproduced with a high degree of precision. We utilized this model to begin to characterize the host immune response to this type of infection. We infected mice via epicutaneous challenge of the skin on the outer ear pinna using Morrow-Brown allergy test needles coated in S. aureus USA300. When mice were challenged in this model, they developed small, purulent, self-clearing lesions with predictable areas of inflammation that mimicked a human infection. CFU in the ear pinna peaked at day 7 before dropping by day 14. The T(h)1 and T(h)17 cytokines gamma interferon (IFN-γ), interleukin-12 (IL-12) p70, tumor necrosis factor alpha (TNF-α), IL-17A, IL-6, and IL-21 were all significantly increased in the draining lymph node of infected mice, and there was neutrophil recruitment to the infection site. In vivo neutrophil depletion demonstrated that neutrophils play a protective role in preventing bacterial dissemination and fatal invasive infection.

摘要

金黄色葡萄球菌是引起社区获得性皮肤和软组织感染(SSTI)的最常见病因之一。虽然大多数社区获得性金黄色葡萄球菌 SSTI 是简单且自行消退的,但仍有一定比例的病例会进展为危及生命的侵袭性感染。目前,金黄色葡萄球菌 SSTI 的动物模型存在两个缺陷:这些模型更能代表医院获得性 SSTI,而不是社区获得性 SSTI,并且它们涉及到难以复制的方法。出于这些原因,我们试图开发一种能够高度精确地重现的社区获得性耐甲氧西林金黄色葡萄球菌 SSTI(CA-MRSA SSTI)的小鼠模型。我们利用该模型开始研究宿主对这种类型感染的免疫反应。我们通过使用金黄色葡萄球菌 USA300 涂层的 Morrow-Brown 过敏试验针经皮挑战外耳耳廓来感染小鼠。当小鼠在该模型中受到感染时,它们会在皮肤上形成小的、脓性的、自行消退的病变,伴有可预测的炎症区域,类似于人类感染。耳廓 CFU 在第 7 天达到峰值,然后在第 14 天下降。感染小鼠引流淋巴结中的 T(h)1 和 T(h)17 细胞因子 γ干扰素(IFN-γ)、白细胞介素-12(IL-12)p70、肿瘤坏死因子-α(TNF-α)、白细胞介素-17A(IL-17A)、白细胞介素-6(IL-6)和白细胞介素-21 均显著增加,并且有中性粒细胞向感染部位募集。体内中性粒细胞耗竭表明中性粒细胞在防止细菌扩散和致命性侵袭性感染方面发挥保护作用。

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