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角质形成细胞内核酸感应的炎症反应。

Inflammatory Response Against Intracellular Sensing of Nucleic Acids in Keratinocytes.

机构信息

Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, Germany.

Deutsches Zentrum für Infektionsforschung (DZIF), Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.

出版信息

Front Immunol. 2022 Feb 24;13:828626. doi: 10.3389/fimmu.2022.828626. eCollection 2022.

DOI:10.3389/fimmu.2022.828626
PMID:35281009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8907419/
Abstract

is one of the clinically most relevant pathogens causing infections. Humans are often exposed to . In approximately one-third of the healthy population it can be found on the skin either for long or short periods as colonizing "commensals", without inducing infections or an inflammatory immune response. While tolerating seems to be limited to certain individuals and time periods in most cases, is tolerated permanently on the skin of almost all individuals without activating overwhelming skin inflammation. To investigate this, we co-cultured a keratinocyte cell line (HaCaT) with viable or to study the differences in the immune activation activated keratinocytes depicted by a profound IL-6 and IL-8 response, whereas did not. Our data indicate that internalization of and the subsequent intracellular sensing of bacterial nucleic acid may be essential for initiating inflammatory response in keratinocytes. Internalized dsRNA activates IL-6 and IL-8 release, but not TNF-α or IFNs by human keratinocytes. This is a non-specific effect of dsRNA, which can be induced using Poly(I:C), as well as RNA from and . However, only viable were able to induce this response as these bacteria and not were actively internalized by HaCaT. The stimulatory effect of seems to be independent of the TLR3, -7 and -8 pathways.

摘要

是临床上最相关的病原体之一,可引起感染。人类经常接触。在大约三分之一的健康人群中,它可以作为定植的“共生体”在皮肤上长期或短期存在,而不会引起感染或炎症免疫反应。虽然在大多数情况下,容忍似乎仅限于某些个体和时间段,但在几乎所有个体的皮肤上都可以容忍,而不会引发压倒性的皮肤炎症。为了研究这一点,我们将角质形成细胞系(HaCaT)与活或共培养,以研究激活的角质形成细胞所表现出的免疫激活的差异,而则没有。我们的数据表明,内化和随后的细菌核酸的细胞内感应可能是角质形成细胞中炎症反应的起始所必需的。内吞双链 RNA 可激活人角质形成细胞释放 IL-6 和 IL-8,但不激活 TNF-α 或 IFN。这是双链 RNA 的非特异性效应,可以使用 Poly(I:C)以及来自和的 RNA 诱导。然而,只有活才能诱导这种反应,因为这些细菌而不是可以被 HaCaT 主动内化。的刺激作用似乎独立于 TLR3、-7 和 -8 途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/5aa6080aceb1/fimmu-13-828626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/ea6139643300/fimmu-13-828626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/84c1e4f4ea6e/fimmu-13-828626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/a082b8ffc294/fimmu-13-828626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/923aff9a2281/fimmu-13-828626-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/5aa6080aceb1/fimmu-13-828626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/ea6139643300/fimmu-13-828626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/84c1e4f4ea6e/fimmu-13-828626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/a082b8ffc294/fimmu-13-828626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/923aff9a2281/fimmu-13-828626-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a122/8907419/5aa6080aceb1/fimmu-13-828626-g005.jpg

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