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唾液酸化脂寡糖有助于猪呼吸道上皮屏障的穿透。

Sialylated Lipooligosaccharide Contributes to Penetration of Porcine Respiratory Epithelial Barrier.

机构信息

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei 430070, China.

出版信息

ACS Infect Dis. 2021 Mar 12;7(3):661-671. doi: 10.1021/acsinfecdis.0c00850. Epub 2021 Mar 1.

Abstract

Pathogens utilize various mechanisms to escape host immunological surveillance, break down different tissue barriers, and cause infection. Sialylation is an important surface modification of bacterial outer membrane components, especially the lipooligosaccharide of Gram-negative bacteria. It is widely involved in multiple microbe-host interactions, such as bacterial virulence regulation, host recognition, and immune evasion. There are some sialylation modifications on the lipooligosaccharide structure of () virulent strains. However, the role of lipooligosaccharide sialylation modification in the process of infection and penetration of the porcine respiratory epithelial barrier is still unclear. In this study, we investigated the role and mechanism of -mediated lipooligosaccharide sialylation in invasion of the host respiratory epithelial barrier. Specifically, -mediated lipooligosaccharide sialylation and sialylated-lipooligosaccharide interacted with Siglec1 on porcine alveolar macrophages 3D4/21 and triggered the subsequent generation of TGFβ1 through Siglec1/Dap12/Syk/p38 signaling cascade. TGFβ1 decreased the tracheal epithelial tight junctions and the expression of extracellular adhesion molecule fibronectin, thus assisting invasion and entry to the respiratory epithelial barrier. Characterizing the potential effects and mechanisms of lipooligosaccharide sialylation-mediated TGFβ1 production would further expand our current knowledge on the pathogenesis of which will contribute to better prevention and control of infection in piglets.

摘要

病原体利用各种机制逃避宿主免疫监视,破坏不同的组织屏障,并引起感染。唾液酸化是细菌外膜成分(尤其是革兰氏阴性菌的脂寡糖)的重要表面修饰方式。它广泛参与多种微生物-宿主相互作用,如细菌毒力调节、宿主识别和免疫逃避。在一些毒力株的脂寡糖结构上存在一些唾液酸化修饰。然而,脂寡糖唾液酸化修饰在 感染和穿透猪呼吸道上皮屏障的过程中的作用尚不清楚。在本研究中,我们研究了 介导的脂寡糖唾液酸化在宿主呼吸道上皮屏障侵袭中的作用和机制。具体来说,介导的脂寡糖唾液酸化与 Siglec1 上的唾液酸化脂寡糖相互作用在猪肺泡巨噬细胞 3D4/21 上,并通过 Siglec1/Dap12/Syk/p38 信号级联触发随后 TGFβ1 的产生。TGFβ1 降低了气管上皮细胞的紧密连接和细胞外黏附分子纤维连接蛋白的表达,从而协助 入侵和进入呼吸道上皮屏障。描述脂寡糖唾液酸化介导的 TGFβ1 产生的潜在作用和机制将进一步扩展我们对 发病机制的现有认识,这将有助于更好地预防和控制仔猪的 感染。

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