CD8(+) T cells restrict Yersinia pseudotuberculosis infection: bypass of anti-phagocytosis by targeting antigen-presenting cells.
CD8(+) T cells restrict Yersinia pseudotuberculosis infection: bypass of anti-phagocytosis by targeting antigen-presenting cells.
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DOI：
10.1371/journal.ppat.1000573
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发表时间：
2009-09
期刊：
影响因子：
6.7
通讯作者：
Isberg RR
中科院分区：
文献类型：
--
作者：
Bergman MA;Loomis WP;Mecsas J;Starnbach MN;Isberg RR
所有耶尔森氏菌都靶向并结合吞噬细胞，但通过将抗吞噬Yop蛋白注射到宿主细胞中来防止细菌的摄取和破坏。在这里，我们提供的证据表明，CD8+ T细胞，典型地消除细胞内病原体，是重要的限制耶尔森氏菌，即使细菌主要是在疾病过程中的细胞外场所发现。在减毒Y.假结核病，缺乏CD8+ T细胞的小鼠比免疫活性小鼠更容易感染。虽然暴露于减毒Y.假结核产生TH1型抗体应答并赋予针对完全毒性细菌攻击的保护，在攻击期间CD8+ T细胞的耗竭严重损害保护性免疫。引人注目的是，缺乏T细胞效应分子穿孔素的小鼠也死于Y。假结核感染鉴于穿孔素的功能是杀死抗原呈递细胞，我们推断细胞死亡标志着细菌相关的宿主细胞被邻近的吞噬细胞内化，从而允许摄取和清除附着的细菌。该模型的支持，溶细胞性T细胞杀伤Y。假结核病相关的宿主细胞导致被细菌和靶细胞的相邻吞噬细胞吞噬，绕过抗吞噬作用。我们的研究结果与细胞介导的免疫反应保护免受细胞外病原体如耶尔森氏菌的新功能一致：穿孔素和CD8+ T细胞对于宿主克服Yops的抗吞噬作用至关重要。致病性耶尔森氏菌是引起多种疾病的细菌，如胃肠炎和鼠疫。耶尔森菌与称为巨噬细胞的专门免疫细胞结合，巨噬细胞试图吞噬和摧毁细菌。这种细菌通过向巨噬细胞注射一种叫做Yops的蛋白质来抵抗破坏，这种蛋白质阻止了吞噬过程。因此耶尔森氏菌作为附着在细胞外的细菌而存活，从而引起疾病。耶尔森氏菌病可以通过免疫接种来预防。在这项研究中，我们确定了一种保护性免疫机制，即称为CD8+ T淋巴细胞的宿主细胞对限制耶尔森氏菌感染很重要。这一观察结果是不寻常的，因为CD8+ T细胞通常可以保护细胞内的病原体：T细胞破坏携带病原体的宿主细胞，从而阻止病原体的复制。我们提出的数据与模型一致，即CD8+ T细胞也可以通过显示T细胞靶向具有细胞外附着耶尔森氏菌的宿主细胞来限制细胞外细菌，从而允许宿主细胞和相关细菌被邻近的巨噬细胞吞噬和清除。
All Yersinia species target and bind to phagocytic cells, but uptake and destruction of bacteria are prevented by injection of anti-phagocytic Yop proteins into the host cell. Here we provide evidence that CD8+ T cells, which canonically eliminate intracellular pathogens, are important for restricting Yersinia, even though bacteria are primarily found in an extracellular locale during the course of disease. In a model of infection with attenuated Y. pseudotuberculosis, mice deficient for CD8+ T cells were more susceptible to infection than immunocompetent mice. Although exposure to attenuated Y. pseudotuberculosis generated TH1-type antibody responses and conferred protection against challenge with fully virulent bacteria, depletion of CD8+ T cells during challenge severely compromised protective immunity. Strikingly, mice lacking the T cell effector molecule perforin also succumbed to Y. pseudotuberculosis infection. Given that the function of perforin is to kill antigen-presenting cells, we reasoned that cell death marks bacteria-associated host cells for internalization by neighboring phagocytes, thus allowing ingestion and clearance of the attached bacteria. Supportive of this model, cytolytic T cell killing of Y. pseudotuberculosis–associated host cells results in engulfment by neighboring phagocytes of both bacteria and target cells, bypassing anti-phagocytosis. Our findings are consistent with a novel function for cell-mediated immune responses protecting against extracellular pathogens like Yersinia: perforin and CD8+ T cells are critical for hosts to overcome the anti-phagocytic action of Yops. Pathogenic Yersinia are bacteria that cause diverse diseases such as gastroenteritis and plague. Yersinia binds to specialized immune cells called macrophages, which attempt to engulf and destroy the bacteria. The bacteria resist destruction by injecting proteins called Yops into macrophages, which stops the engulfment process. Yersinia thus survives as attached but extracellular bacteria to cause disease. Yersinia disease can be prevented by immunization. In this study, we identified one mechanism of protective immunity—that host cells called CD8+ T lymphocytes are important to restrict Yersinia infection. This observation is unusual because CD8+ T cells generally protect against intracellular pathogens: T cells destroy the host cell harboring the pathogen, thus preventing the pathogen's replication. We present data consistent with the model that CD8+ T cells can also restrict extracellular bacteria by showing that T cells target host cells with extracellularly attached Yersinia, thus allowing the host cells and associated bacteria to be engulfed and removed by neighboring macrophages.
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影响因子：
3.1
作者：
AUTENRIETH, IB;BEER, M;HEESEMANN, J
通讯作者：
HEESEMANN, J
影响因子：
28.2
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ABBOTT, M;GALLOWAY, A;CUNNINGHAM, JL
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影响因子：
3
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Autenrieth, IB;Firsching, R
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影响因子：
3.1
作者：
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通讯作者：
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影响因子：
15.3
作者：
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通讯作者：
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