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首页> 外文期刊>Infection and immunity >Tumor Necrosis Factor Alpha and Gamma Interferon, but Not Hemorrhage or Pathogen Burden, Dictate Levels of Protective Fibrin Deposition during Infection
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Tumor Necrosis Factor Alpha and Gamma Interferon, but Not Hemorrhage or Pathogen Burden, Dictate Levels of Protective Fibrin Deposition during Infection

机译：肿瘤坏死因子α和γ干扰素，而不是出血或病原体负担，决定了感染过程中保护性纤维蛋白沉积的水平

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While coagulation often causes pathology during infectious disease, we recently demonstrated that fibrin, a product of the coagulation pathway, performs a critical protective function during acute toxoplasmosis (L. L. Johnson, K. N. Berggren, F. M. Szaba, W. Chen, and S. T. Smiley, J. Exp. Med. >197:801-806, 2003). Here, we investigate the mechanisms regulating the formation of this protective fibrin. Through comparisons of Toxoplasma-infected wild-type and cytokine-deficient mice we dissociate, for the first time, the relative fibrin-regulating capacities of pathogen products, host cytokines, and infection-stimulated hemorrhage. Remarkably, neither the pathogen burden nor hemorrhage is a primary regulator of fibrin levels. Rather, two type 1 cytokines exert dominant and counterregulatory roles: tumor necrosis factor alpha (TNF-α), acting via the type 1 TNF-α receptor, promotes fibrin deposition, while gamma interferon (IFN-γ), acting via STAT1 and IFN-γ receptors expressed on radioresistant cells, suppresses fibrin deposition. These findings have important clinical implications, as they establish that cytokines known to regulate pathological coagulation also dictate levels of protective fibrin deposition. We present a novel model depicting mechanisms by which the immune system can destroy infected tissue while independently restraining hemorrhage and promoting tissue repair through the deliberate deposition of protective fibrin.
机译：虽然凝血通常在传染病期间引起病理变化，但我们最近证明了凝血途径的产物纤维蛋白在急性弓形体病期间起着至关重要的保护功能（LL Johnson，KN Berggren，FM Szaba，W.Chen，and ST Smiley，J.实验医学> 197： 801-806，2003年）。在这里，我们研究调节这种保护性纤维蛋白形成的机制。通过比较弓形虫感染的野生型和细胞因子缺陷型小鼠，我们首次分离了病原体产物，宿主细胞因子和感染引起的出血的相对纤维蛋白调节能力。值得注意的是，病原体负担和出血都不是血纤蛋白水平的主要调节剂。相反，两种1型细胞因子发挥主要作用和反调节作用：通过1型TNF-α受体起作用的肿瘤坏死因子α（TNF-α）促进纤维蛋白沉积，而通过STAT1和IFN起作用的γ干扰素（IFN-γ）。在抗辐射细胞上表达的-γ受体抑制纤维蛋白沉积。这些发现具有重要的临床意义，因为它们确定了已知可调节病理性凝血的细胞因子也决定了保护性纤维蛋白沉积的水平。我们提出了一个新颖的模型，描述了免疫系统可以破坏感染的组织，同时独立地抑制出血并通过故意沉积保护性纤维蛋白促进组织修复的机制。

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