Bacterial membrane vesicles shape Staphylococcus aureus skin colonization and induction of innate immune responses

Bacterial membrane vesicles shape Staphylococcus aureus skin colonization and induction of innate immune responses
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细菌膜囊泡形状金黄色葡萄球菌皮肤定植和诱导先天免疫反应

DOI:
10.1111/exd.14478
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发表时间:
2022
影响因子:
3.6
通讯作者:
Schittek B
Schittek B
中科院分区:
医学2区
文献类型:
--
作者:
Staudenmaier L;Focken J;Schlatterer K;Kretschmer D;Schittek B

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金黄色葡萄球菌在特应性皮炎(AD)患者的皮肤上大量定植,导致皮肤炎症。金黄色葡萄球菌产生毒力因子,将其与表皮葡萄球菌和鲁顿葡萄球菌等共生皮肤细菌区分开来。然而,目前还不清楚这些毒力因素中哪些对AD的影响最大。膜泡(MVS)由病原菌释放,在细菌毒力因子等效应物的长距离传递中可能起着重要的作用。我们发现,MVS也是由皮肤共生体释放的,其量和膜脂的量与致病金黄色葡萄球菌相似。有趣的是,来自皮肤共生体的MVS可以通过调节人类皮肤来增强防御能力,从而防止金黄色葡萄球菌的侵袭。相反,金黄色葡萄球菌释放的微血管能够诱导原代人角质形成细胞CXCL8和肿瘤坏死因子-α,募集中性粒细胞,并诱导中性粒细胞胞外陷阱,从而促进金黄色葡萄球菌的定植。CXCL8的诱导依赖于TLR2和NFkB,其诱导程度与MVS的膜脂和蛋白A含量有关。有趣的是,与来自非皮损部位的菌株相比,来自AD患者皮损皮肤的金黄色葡萄球菌的MVS显示出更高的膜脂和蛋白A含量,并具有更强的促炎潜力。我们的数据强调了宿主和细菌来源的因素在金黄色葡萄球菌定植中的复杂相互作用,以及细菌来源的MVS及其膜脂和蛋白A含量在皮肤炎症疾病中的重要作用。
Staphylococcus aureuscolonization is abundant on the skin of atopic dermatitis (AD) patients where it contributes to skin inflammation.S.aureusproduces virulence factors that distinguish it from commensal skin bacteria such asS.epidermidisandS.lugdunensis. However, it has remained unclear, which of these virulence factors have the strongest impact on AD. Membrane vesicles (MVs) are released by pathogenic bacteria and might play an essential role in the long‐distance delivery of bacterial effectors such as virulence factors. We show that MVs are also released by skin commensals in a similar quantity and membrane lipid amount as those from pathogenicS.aureus. Interestingly, MVs from skin commensals can protect againstS.aureusskin colonization by conditioning human skin for enhanced defence. In contrast, MVs released byS.aureusare able to induce CXCL8 and TNF‐α in primary human keratinocytes, recruit neutrophils and induce neutrophil extracellular traps, which enhanceS.aureusskin colonization. CXCL8 induction is TLR2‐ and NFkB‐dependent and the induction level correlates with the membrane lipid and protein A content of the MVs. Interestingly, MVs ofS.aureusstrains from the lesional skin of AD patients show an enhanced membrane lipid and protein A content compared to the strains from the non‐lesional sites and have an enhanced proinflammatory potential. Our data underline the complex interplay in host‐ and bacterial derived factors inS.aureusskin colonization and the important role of bacterial derived MVs and their membrane lipid and protein A content in skin inflammatory disorders.
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发表时间: 2017-01-01
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