Transforming growth factor beta and CD25 are important for controlling systemic dissemination following Yersinia enterocolitica infection of the gut.
Transforming growth factor beta and CD25 are important for controlling systemic dissemination following Yersinia enterocolitica infection of the gut.
复制标题
转化生长因子β和CD25对于控制肠道小肠结肠炎耶尔森菌感染后的全身传播非常重要。
DOI：
10.1128/iai.00203-10
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发表时间：
2010
影响因子：
3.1
通讯作者：
Dube,PeterH
中科院分区：
文献类型：
--
作者：
Zhong,Youmin;Cantwell,Angelene;Dube,PeterH
侵入性细菌病原体对肠道的感染导致强烈的炎症反应，如果不加以控制，可能导致自身免疫性疾病和其他后遗症。免疫系统如何控制炎症并限制急性细菌感染期间对宿主的附带损害还知之甚少。在此，我们报道了在肠道致病菌小肠结肠炎耶尔森菌感染前，通过抗体介导的转化生长因子β（TGF-β）中和作用，平均死亡时间缩短了1天（P= 0.001），导致肝脏和肺的快速定植，并与炎症组织病理学的恶化有关。在小肠结肠炎耶尔森氏菌感染过程中，CD 4+细胞是派伊尔集合淋巴结、肠系膜淋巴结和脾脏中TGF-β转录的新来源。相应地，在卵清蛋白T细胞受体限制性OT-II小鼠中，耶尔森氏菌感染后，CD 4 + CD 25 + Foxp 3+和TGF-β+ T调节细胞（T-lymphocytes，T-lymphocytes）的抗原特异性和非依赖性扩增均减少。抗CD 25治疗对CD 25的功能性失活导致更快的死亡，细菌传播到肝脏和肺部，并加剧炎症组织病理学，与TGF-β中和期间观察到的情况相似。总而言之，这些数据表明，由T-β产生的TGF-β在肠道侵入性细菌感染的急性期期间限制细菌方面是重要的。这些数据扩展了T-T细胞的作用，除了T-T细胞在慢性感染、免疫稳态控制和自身免疫性疾病中的既定作用外，还包括在急性感染期间缓和炎症。
Infection of the gut by invasive bacterial pathogens leads to robust inflammatory responses that if left unchecked can lead to autoimmune disease and other sequelae. How the immune system controls inflammation and limits collateral damage to the host during acute bacterial infection is poorly understood. Here, we report that antibody-mediated neutralization of transforming growth factor β (TGF-β) prior to infection with the model enteric pathogenYersinia enterocoliticareduces the mean time to death by 1 day (P= 0.001), leads to rapid colonization of the liver and lung, and is associated with exacerbation of inflammatory histopathology. DuringYersinia enterocoliticainfection CD4+cells are the source ofde novoTGF-β transcription in the Peyer's patches, mesenteric lymph nodes, and spleen. Correspondingly there is both antigen-specific and -independent expansion of CD4+CD25+Foxp3+and TGF-β+T-regulatory cells (T-regs) afterYersiniainfection that is reduced in ovalbumin T-cell receptor-restricted OT-II mice. Functional inactivation of CD25 by anti-CD25 treatment results in more rapid death, dissemination of the bacteria to the liver and lungs, and exacerbated inflammatory histopathology, similar to what is seen during TGF-β neutralization. Altogether, these data suggest that TGF-β produced by T-regs is important in restricting bacteria during the acute phase of invasive bacterial infection of the gut. These data expand the roles of T-regs to include tempering inflammation during acute infection in addition to the well-established roles of T-regs in chronic infection, control of immune homeostasis, and autoimmune disease.