Activation of apoptosis by Salmonella pathogenicity island-1 effectors through both intrinsic and extrinsic pathways in Salmonella-infected macrophages
Activation of apoptosis by Salmonella pathogenicity island-1 effectors through both intrinsic and extrinsic pathways in Salmonella-infected macrophages
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DOI：
10.1016/j.jmii.2020.02.008
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发表时间：
2021-08-20
影响因子：
7.4
通讯作者：
Chiu, Cheng-Hsun
中科院分区：
文献类型：
--
作者：
Lin, Hsin-Hung;Chen, Hsiu-Ling;Chiu, Cheng-Hsun
背景：伤寒沙门氏菌是一种非伤寒性食源性病原体，可引起人类急性小肠结肠炎、菌血症、肠外局灶性感染。沙门氏菌致病性岛1和2 （SPI-1和SPI-2）侵入宿主细胞质，在含沙门氏菌的空泡中存活，诱导细胞凋亡。本研究旨在更好地了解沙门氏菌感染巨噬细胞凋亡的机制。方法：采用鼠伤寒沙门氏菌SL1344研究THP-1单核细胞源性巨噬细胞对沙门菌感染的内源性和外源性凋亡途径。结果：在沙门氏菌感染的巨噬细胞中，激活的caspase-3诱导的凋亡途径，包括外源性（caspase-8介导）和内源性（caspase-9介导）途径。构建TLR-4和TLR-5功能障碍的THP-1细胞和沙门氏菌SPI-1和SPI-2突变体，以确定与细胞程序性死亡相关的基因在巨噬细胞中的作用。沙门氏菌通过TLR-4和TLR-5信号通路诱导THP-1巨噬细胞中Caspase-3的激活。我们还发现SPI-1结构蛋白PrgH和效应物SipB和SipD，而不是SPI-2结构蛋白SsaV，可以通过caspase-3激活诱导沙门氏菌感染细胞凋亡，并减少炎症标志物TNF-a的分泌。两种效应器还能减少NF-kB p65亚基向细胞核的易位和TNF-a的表达，从而减轻炎症反应。结论：非伤寒沙门氏菌通过表达SPI-1诱导巨噬细胞凋亡，从而减少炎症细胞因子的产生。这种宿主-病原体相互作用的机制可以解释为什么沙门氏菌在儿童血液感染中通常表现为隐蔽性菌血症和较少的全身炎症反应综合征。台湾省微生物学会版权所有由爱思唯尔台湾有限责任公司发布。这是一篇基于CC by - nc-nd许可（http://creativecommons.org/licenses/bync-nd/4.0/）的开放获取文章。
Background: Salmonella enterica serovar Typhimurium, a non-typhoidal food borne pathogen, causes acute enterocolitis, bacteremia, extraintestinal focal infections in humans. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) contribute to invading into host cellular cytosol, residing in Salmonella-containing vacuoles for intracellular survival, and inducing cellular apoptosis. This study aimed to better understand the mechanism underlying apoptosis in Salmonella-infected macrophages. Methods: S. Typhimurium SL1344 was used to evaluate extrinsic and intrinsic apoptosis pathways in THP-1 monocyte-derived macrophages in response to Salmonella infection. Results: Activated caspase-3-induced apoptosis pathways, including extrinsic (caspase-8mediated) and intrinsic (caspase-9-mediated) pathways, in Salmonella-infected macrophages were verified. THP-1 cells with dysfunction of TLR-4 and TLR-5 and Salmonella SPI-1 and SPI-2 mutants were constructed to identify the roles of the genes associated with programmed cell death in the macrophages. Caspase-3 activation in THP-1 macrophages was induced by Salmonella through TLR-4 and TLR-5 signaling pathways. We also identified that SPI-1 structure protein PrgH and effectors SipB and SipD, but not SPI-2 structure protein SsaV, could induce apoptosis via caspase-3 activation and reduce the secretion of inflammation marker TNF-a in the Salmonella-infected cells. The two effectors also reduced the translocation of the p65 subunit of NF-kB into the nucleus and the expression of TNF-a, and then inflammation was diminished. Conclusion: Non-typhoid Salmonella induced apoptosis of macrophages and thereby reduced inflammatory cytokine production through the expression of SPI-1. This mechanism in host-pathogen interaction may explain why Salmonella usually manifests as occult bacteremia with less systemic inflammatory response syndrome in the bloodstream infection of children. Copyright 2020, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).