Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo.
Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo.
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DOI：
10.1371/journal.ppat.1006925
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发表时间：
2018-03
期刊：
影响因子：
6.7
通讯作者：
Hornef M
中科院分区：
文献类型：
--
作者：
Zhang K;Riba A;Nietschke M;Torow N;Repnik U;Pütz A;Fulde M;Dupont A;Hensel M;Hornef M
由沙门氏菌致病岛（SPI）1编码的3型分泌系统（T3SS）转运的效应分子在人类沙门氏菌感染的发病机制中起关键作用。它们促进非吞噬性肠细胞的内化，使肠上皮成为感染的进入部位。它们在体内的功能仍然不明确，由于缺乏一个合适的动物模型，允许可视化的上皮内沙门氏菌。在这里，我们利用我们的新的新生小鼠模型，并分析了各种细菌突变体和报告菌株以及基因缺陷小鼠。我们的研究结果表明，关键的，但多余的作用，SopE2和SiPA的肠上皮细胞的侵袭，转录刺激和粘膜易位的先决条件在体内。相反，复制性上皮内内体隔室的产生需要SipA和SopE2或SipA和SopB的协同作用，但不依赖于SopA或宿主MyD88信号传导。上皮内生长对全身扩散没有关键影响。我们的研究结果定义了SPI1-T3SS效应分子在体内肠上皮细胞侵袭和上皮内增殖过程中的作用，为沙门氏菌感染的早期过程提供了新的见解。非伤寒沙门氏菌是全球胃肠炎的主要病原体。发病机制的标志是它们凭借其3型分泌系统主动侵入肠上皮的能力，所述3型分泌系统将细菌毒力因子直接递送到宿主细胞胞质溶胶中。这些毒力因子在肠上皮细胞进入和上皮内生长过程中的作用仅在体外进行了研究，因为先前在小动物中建立的体内模型不允许上皮内沙门氏菌的可视化。然而，永生化细胞系缺乏覆盖的粘液层，最终的细胞谱系分化，顶-基底侧极化以及沿隐窝绒毛轴的连续迁移沿着，因此在沙门氏菌体内感染过程中毒力因子的作用在很大程度上仍然不确定。在这里，我们利用我们新的新生小鼠感染模型，并首次系统地分析了沙门氏菌毒力因子对肠上皮细胞侵袭和上皮内生长的重要性。
Effector molecules translocated by the Salmonella pathogenicity island (SPI)1-encoded type 3 secretion system (T3SS) critically contribute to the pathogenesis of human Salmonella infection. They facilitate internalization by non-phagocytic enterocytes rendering the intestinal epithelium an entry site for infection. Their function in vivo has remained ill-defined due to the lack of a suitable animal model that allows visualization of intraepithelial Salmonella. Here, we took advantage of our novel neonatal mouse model and analyzed various bacterial mutants and reporter strains as well as gene deficient mice. Our results demonstrate the critical but redundant role of SopE2 and SipA for enterocyte invasion, prerequisite for transcriptional stimulation and mucosal translocation in vivo. In contrast, the generation of a replicative intraepithelial endosomal compartment required the cooperative action of SipA and SopE2 or SipA and SopB but was independent of SopA or host MyD88 signaling. Intraepithelial growth had no critical influence on systemic spread. Our results define the role of SPI1-T3SS effector molecules during enterocyte invasion and intraepithelial proliferation in vivo providing novel insight in the early course of Salmonella infection. Non-typhoidal Salmonella represent a major causative agent of gastroenteritis worldwide. Hallmark of the pathogenesis is their ability to actively invade the intestinal epithelium by virtue of their type 3 secretion system that delivers bacterial virulence factors directly into the host cell cytosol. The role of these virulence factors during enterocyte entry and intraepithelial growth has only been investigated in vitro since the previously established in vivo models in small animals did not allow visualization of intraepithelial Salmonella. However, immortalized cell lines lack the overlaying mucus layer, final cell lineage differentiation, apical-basolateral polarization as well as continuous migration along the crypt villus axis and thus the role of virulence factors during the Salmonella infection in vivo has remained largely undefined. Here, we took advantage of our novel neonatal mouse infection model and for the first time systematically analyzed the importance of Salmonella virulence factors for enterocyte invasion and intraepithelial growth.
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影响因子：
6.7
作者：
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通讯作者：
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通讯作者：
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