Yersinia has a tropism for B and T cell zones of lymph nodes that is independent of the type III secretion system.
Yersinia has a tropism for B and T cell zones of lymph nodes that is independent of the type III secretion system.
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DOI：
10.1371/journal.ppat.0020086
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发表时间：
2006-09
期刊：
影响因子：
6.7
通讯作者：
Mecsas J
中科院分区：
文献类型：
--
作者：
Balada-Llasat JM;Mecsas J
致病性耶尔森菌对淋巴组织有明显的趋向性，并携带一种毒力质粒，该质粒编码III型分泌系统pTTSS，该系统可将Yops转运到宿主细胞中。Yops是阻止巨噬细胞和中性粒细胞吞噬的关键毒力因子，缺乏一种或多种Yops的耶尔森氏菌突变体在淋巴组织、肝脏和胃肠道中存在生存缺陷。然而，本研究表明，缺乏pTTSS的假结核杆菌（Yptb）突变体在肠系膜淋巴结（MLN）中的存活率与野生型（WT）相同，甚至更好。pTTSS突变体感染引起淋巴结炎，伴少量坏死，而WT结核感染引起淋巴结炎伴多发坏死化脓性灶。庆大霉素保护实验和MLN的显微镜检查显示pTTSS突变体位于皮层和副皮层的B淋巴细胞和T淋巴细胞附近的细胞外。wtyptb在坏死区域与中性粒细胞和巨噬细胞相邻，在炎症较轻的区域与B淋巴细胞和T淋巴细胞相邻。为了确定淋巴细胞是否保护pTTSS突变体免受吞噬细胞的侵害，Rag1−/−小鼠感染了pTTSS突变体或WT Yptb。在Rag1−/−小鼠的MLN中，pTTSS突变体而非WT突变体的生存受到损害，这表明淋巴细胞富集区构成了pTTSS突变体的保护生态位。最后，我们发现入侵蛋白和染色体编码的TTSS不是MLN中Yptb存活所必需的。综上所述，染色体编码因子足以在MLN的皮层和副皮层进行Yptb复制；pTTSS使耶尔森氏菌能够在淋巴结富含吞噬细胞的区域存活，并扩散到其他组织。致病菌耶尔森氏菌合成一种被称为III型分泌系统的装置，该系统将细菌蛋白Yops从细菌中转运到重要的免疫细胞中，如巨噬细胞和中性粒细胞。正常情况下，巨噬细胞和中性粒细胞通过摄取细菌来控制细菌感染；然而，Yops使这些免疫细胞失活，这反过来又使耶尔森氏菌在细胞外复制，并在许多类型的组织中引起疾病。致病性耶尔森氏菌经常在受感染宿主的淋巴结中发现，Yops对于细菌复制和引起淋巴结疾病很重要，因为缺乏Yops的耶尔森氏菌突变体不能有效地定殖淋巴结。令人惊讶的是，作者发现缺乏III型分泌系统的假结核耶尔森菌在肠系膜淋巴结上定植，并在淋巴细胞旁的细胞外存活。然而，在缺乏淋巴细胞的小鼠中，III型分泌突变体不能存活，而野生型耶尔森菌却能存活。作者的研究结果表明，其他细菌因素足以使耶尔森氏菌在肠系膜淋巴结（MLN）定植，淋巴细胞为缺乏III型分泌系统的耶尔森氏菌菌株提供保护生态位。这些在肠系膜淋巴结中存在至少5天的无毒突变株，可能被用作预防耶尔森氏菌感染的减毒活疫苗，或作为其他抗原的载体。
Pathogenic Yersinia have a pronounced tropism for lymphatic tissues and harbor a virulence plasmid that encodes a type III secretion system, pTTSS, that transports Yops into host cells. Yops are critical virulence factors that prevent phagocytosis by macrophages and neutrophils and Yersinia mutants lacking one or more Yops are defective for survival in lymphatic tissues, liver, and gastrointestinal tract. However, here we demonstrate that Y. pseudotuberculosis (Yptb) mutants lacking the pTTSS survived as well as or better than wild-type (WT) Yptb in the mesenteric lymph nodes (MLN). Infection with pTTSS mutants caused lymphadenitis with little necrosis, whereas infection with WT Yptb provoked lymphadenitis with multiple necrotic suppurative foci. Gentamicin protection assays and microscopic examination of the MLN revealed that pTTSS mutants resided extracellularly adjacent to B and T lymphocytes in the cortex and paracortex. WT Yptb was found extracellularly adjacent to neutrophils and macrophages in necrotic areas and adjacent to B and T lymphocytes in less-inflamed areas. To determine whether lymphocytes protected pTTSS mutants from phagocytic cells, Rag1−/− mice were infected with pTTSS mutants or WT Yptb. pTTSS mutants but not WT, were impaired for survival in MLN of Rag1−/− mice, suggesting that lymphocyte-rich regions constitute a protective niche for pTTSS mutants. Finally, we show that invasin and the chromosomally encoded TTSS were not required for Yptb survival in MLN. In summary, chromosomally encoded factors are sufficient for Yptb replication in the cortex and paracortex of MLN; the pTTSS enables Yersinia to survive within phagocyte-rich areas of lymph nodes, and spread to other tissues. The pathogenic bacteria, Yersinia, synthesize an apparatus called a type III secretion system, which transports bacterial proteins, Yops, from the bacteria into important immune cells, such as macrophages and neutrophils. Normally, macrophages and neutrophils control bacterial infections by ingesting the bacteria; however, the Yops inactivate these immune cells, which in turn, enable Yersinia to replicate extracellularly and cause disease in many types of tissues. Pathogenic Yersinia are frequently found in lymph nodes of infected hosts, and the Yops are important for the bacteria to replicate and cause disease in lymph nodes since Yersinia mutants that lack Yops do not colonize lymph nodes efficiently. Surprisingly, the authors found that Yersinia pseudotuberculosis lacking the type III secretion system colonizes the mesenteric lymph nodes and survives extracellularly next to lymphocytes. However, in mice lacking lymphocytes, the type III secretion mutants did not survive although wild-type Yersinia did. The authors' findings reveal that other bacterial factors are sufficient for mesenteric lymph node (MLN) colonization of Yersinia and that lymphocytes provide a protective niche for Yersinia strains lacking the type III secretion system. Potentially, these avirulent mutant strains, which persist for at least 5 d in the mesenteric lymph nodes, could be used as live attenuated vaccines to protect against Yersinia infections, or as carriers of other antigens.
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影响因子：
36.8
作者：
BRUBAKER, RR
通讯作者：
BRUBAKER, RR
影响因子：
15.3
作者：
Barnes, Penelope D.;Bergman, Molly A.;Isberg, Ralph R.
通讯作者：
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影响因子：
3.2
作者：
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通讯作者：
GOGUEN, JD
影响因子：
64.5
作者：
ISBERG, RR;LEONG, JM
通讯作者：
LEONG, JM
影响因子：
3.6
作者：
BOLIN, I;WOLFWATZ, H
通讯作者：
WOLFWATZ, H