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传播激活免疫通路,同时抑制皮肤伤口愈合。

Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin.

作者信息

Underwood Jacob, Harvey Cristina, Lohstroh Elizabeth, Pierce Branden, Chambers Cross, Guzman Valencia Stephanie, Oliva Chávez Adela S

机构信息

Department of Entomology, Texas A&M University, College Station, TX 77845, USA.

Navy Entomology Center of Excellence, United States Navy, Jacksonville, FL 32212, USA.

出版信息

Life (Basel). 2022 Nov 24;12(12):1965. doi: 10.3390/life12121965.

DOI:10.3390/life12121965
PMID:36556330
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9781593/
Abstract

the causative agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular bacterium transmitted by the bite of black-legged ticks, . The main host cells in vertebrates are neutrophils. However, the first site of entry is in the skin during tick feeding. Given that the initial responses within skin are a crucial determinant of disease outcome in vector-borne diseases, we used a non-biased approach to characterize the transcriptional changes that take place at the bite during feeding and transmission. Experimentally infected ticks were allowed to feed for 3 days on C57BL/6J mice to allow bacterial transmission and establishment. Skin biopsies were taken from the attachment site of uninfected ticks and -infected ticks. Skin without ticks (intact skin) was used as baseline. RNA was isolated and sequenced using next-generation sequencing (NGS). The differentially expressed genes were used to identify over-represented pathways by gene ontology (GO) and pathway enrichment (PE). transmission resulted in the activation of interferon signaling and neutrophil chemotaxis pathways in the skin. Interestingly, it also led to the downregulation of genes encoding extracellular matrix (ECM) components, and upregulation of metalloproteinases, suggesting that delays wound healing responses and may increase vascular permeability at the bite site.

摘要

人粒细胞无形体病(HGA)的病原体是一种专性细胞内细菌,通过黑腿蜱的叮咬传播。脊椎动物中的主要宿主细胞是中性粒细胞。然而,最初的进入部位是蜱虫叮咬时的皮肤。鉴于皮肤内的初始反应是媒介传播疾病疾病结局的关键决定因素,我们采用了一种无偏倚的方法来表征蜱虫取食和传播过程中叮咬部位发生的转录变化。将实验感染的蜱虫放在C57BL/6J小鼠身上取食3天,以实现细菌传播和定植。从未感染蜱虫和感染蜱虫的附着部位采集皮肤活检样本。没有蜱虫的皮肤(完整皮肤)用作基线。使用下一代测序(NGS)分离并测序RNA。通过基因本体论(GO)和通路富集(PE),利用差异表达基因来识别过度富集的通路。传播导致皮肤中干扰素信号传导和中性粒细胞趋化通路的激活。有趣的是,它还导致编码细胞外基质(ECM)成分的基因下调,以及金属蛋白酶上调,这表明其会延迟伤口愈合反应,并可能增加叮咬部位的血管通透性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/d088a4321e86/life-12-01965-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/4aba423a927c/life-12-01965-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/6f5238644281/life-12-01965-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/dc213d8e2e5a/life-12-01965-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/204baef1f912/life-12-01965-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/61f872b1dc8b/life-12-01965-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/d088a4321e86/life-12-01965-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/4aba423a927c/life-12-01965-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/6f5238644281/life-12-01965-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/dc213d8e2e5a/life-12-01965-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/204baef1f912/life-12-01965-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/61f872b1dc8b/life-12-01965-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3e2/9781593/d088a4321e86/life-12-01965-g006.jpg

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本文引用的文献

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C10orf99/GPR15L Regulates Proinflammatory Response of Keratinocytes and Barrier Formation of the Skin.C10orf99/GPR15L 调控角质形成细胞的促炎反应和皮肤屏障的形成。
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Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection.
蜱细胞外囊泡使节肢动物能够进食,并促进细菌感染的不同结果。
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