Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression.
Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression.
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有毒的志贺氏菌Flexneri通过操纵抗菌肽基因表达来颠覆宿主的先天免疫反应。
DOI：
10.1084/jem.20071698
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发表时间：
2008-05-12
期刊：
影响因子：
--
通讯作者：
Pédron T
中科院分区：
文献类型：
--
作者：
Sperandio B;Regnault B;Guo J;Zhang Z;Stanley SL Jr;Sansonetti PJ;Pédron T
抗菌因子是天然免疫的有效防御成分，对肠道内环境的稳定和对病原体的保护起着至关重要的作用。在这项研究中，我们报道了在体外感染极化的人肠道细胞后，强毒福氏志贺氏菌抑制了几个编码抗菌阳离子多肽的基因的转录，特别是我们证明对福氏志贺菌特别有效的人β防御素HBD-3。这是有针对性的生存战略的一个例子。我们还发现MxiE细菌调节因子负责这一专门的调节过程，该调节因子控制着一组注入宿主细胞的毒力质粒编码的效应子，并调节固有信号。在体内，在人类异种肠道移植模型中，我们在转录和翻译水平上证实，存在一个专门的MxiE依赖系统，使福氏志贺氏菌能够抑制抗菌阳离子多肽的表达，并促进其向肠道隐窝的更深层次进展。我们证明，这个系统还能够下调额外的先天免疫基因，如趋化因子CCL20基因，导致树突状细胞向感染组织的固有层募集。因此，福氏志贺氏菌已经制定了一种专门的策略来削弱先天免疫来管理其在肠道中的生存和定植能力。
Antimicrobial factors are efficient defense components of the innate immunity, playing a crucial role in the intestinal homeostasis and protection against pathogens. In this study, we report that upon infection of polarized human intestinal cells in vitro, virulent Shigella flexneri suppress transcription of several genes encoding antimicrobial cationic peptides, particularly the human β-defensin hBD-3, which we show to be especially active against S. flexneri. This is an example of targeted survival strategy. We also identify the MxiE bacterial regulator, which controls a regulon encompassing a set of virulence plasmid-encoded effectors injected into host cells and regulating innate signaling, as being responsible for this dedicated regulatory process. In vivo, in a model of human intestinal xenotransplant, we confirm at the transcriptional and translational level, the presence of a dedicated MxiE-dependent system allowing S. flexneri to suppress expression of antimicrobial cationic peptides and promoting its deeper progression toward intestinal crypts. We demonstrate that this system is also able to down-regulate additional innate immunity genes, such as the chemokine CCL20 gene, leading to compromised recruitment of dendritic cells to the lamina propria of infected tissues. Thus, S. flexneri has developed a dedicated strategy to weaken the innate immunity to manage its survival and colonization ability in the intestine.
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DOI：
10.1016/j.bbrc.2004.06.049
发表时间：
2004-07-30
影响因子：
3.1
作者：
Jang, BC;Lim, KJ;Suh, SI
通讯作者：
Suh, SI
影响因子：
3.6
作者：
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通讯作者：
Parsot, C
影响因子：
30.5
作者：
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通讯作者：
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影响因子：
15.9
作者：
LEHRER, RI;BARTON, A;SELSTED, ME
通讯作者：
SELSTED, ME
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP