Th17 Cells Are More Protective Than Th1 Cells Against the Intracellular Parasite Trypanosoma cruzi.
Th17 Cells Are More Protective Than Th1 Cells Against the Intracellular Parasite Trypanosoma cruzi.
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DOI：
10.1371/journal.ppat.1005902
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发表时间：
2016-10
期刊：
影响因子：
6.7
通讯作者：
Hoft DF
中科院分区：
文献类型：
--
作者：
Cai CW;Blase JR;Zhang X;Eickhoff CS;Hoft DF
Th17细胞是CD4+ T细胞的一个亚群，已知在许多自身免疫性疾病的发病机制以及对一些细胞外细菌和真菌的防御中发挥核心作用。然而，Th17细胞不被认为对细胞内感染有显著的功能。与这种模式相反，我们发现Th17细胞对克氏锥虫（一种导致恰加斯病的细胞内原生动物寄生虫）提供强大的保护。Th17细胞甚至比Th1细胞具有更强的抗克氏T型虫相关死亡的保护作用，传统上认为Th1细胞是CD4+ T细胞亚群，对克氏T型虫和其他细胞内微生物的免疫最重要。在机制上，Th17细胞可以通过il - 17a依赖性诱导NADPH氧化酶直接保护被感染细胞，参与吞噬细胞呼吸爆发反应，并通过il -21依赖性激活CD8+ T细胞提供间接帮助。这些新的Th17细胞介导的对细胞内免疫重要的直接保护和间接辅助作用的发现突出了Th17细胞作用的多样性，并增加了对克氏t型病毒保护性免疫的理解，有助于开发恰加斯病的治疗方法和疫苗。慢性感染细胞内寄生虫克氏锥虫可导致恰加斯病，这是一种在20多个国家流行的疾病，可导致危及生命的心脏和胃肠功能障碍。虽然已知CD4+ Th1细胞对克氏T细胞感染具有保护作用，但对其他CD4+ T细胞亚群的作用知之甚少。我们证明CD4+ Th17细胞对T. cruzi感染也具有高度的保护作用，甚至在保护T. cruzi相关死亡方面优于Th1细胞，尽管标准概念认为Th17细胞仅在防御细胞外病原体中起重要作用。新发现的Th17细胞比Th1细胞对克氏t型病毒感染具有更强的保护作用，这增加了我们对这种主要人类病原体的有利免疫反应的理解，并可能指导未来疫苗开发的努力。
Th17 cells are a subset of CD4+ T cells known to play a central role in the pathogenesis of many autoimmune diseases, as well as in the defense against some extracellular bacteria and fungi. However, Th17 cells are not believed to have a significant function against intracellular infections. In contrast to this paradigm, we have discovered that Th17 cells provide robust protection against Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas disease. Th17 cells confer significantly stronger protection against T. cruzi-related mortality than even Th1 cells, traditionally thought to be the CD4+ T cell subset most important for immunity to T. cruzi and other intracellular microorganisms. Mechanistically, Th17 cells can directly protect infected cells through the IL-17A-dependent induction of NADPH oxidase, involved in the phagocyte respiratory burst response, and provide indirect help through IL-21-dependent activation of CD8+ T cells. The discovery of these novel Th17 cell-mediated direct protective and indirect helper effects important for intracellular immunity highlights the diversity of Th17 cell roles, and increases understanding of protective T. cruzi immunity, aiding the development of therapeutics and vaccines for Chagas disease. Chronic infection with the intracellular parasite Trypanosoma cruzi results in Chagas disease, an illness endemic in more than 20 countries that leads to life-threatening cardiac and gastrointestinal dysfunction. Although CD4+ Th1 cells are known to be protective against T. cruzi infection, less is known about the role of other CD4+ T cell subsets. We demonstrate that CD4+ Th17 cells are also highly protective against T. cruzi infection, even outperforming Th1 cells in protection from T. cruzi-related death, despite the standard conception that Th17 cells are only important in the defense against extracellular pathogens. The novel discovery that Th17 cells are significantly more protective than Th1 cells against T. cruzi infection has increased our understanding of the advantageous immune responses for this major human pathogen, and may guide future efforts toward vaccine development.
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影响因子：
30.5
作者：
Bermejo, Daniela A.;Jackson, Shaun W.;Gorosito-Serran, Melisa;Acosta-Rodriguez, Eva V.;Amezcua-Vesely, Maria C.;Sather, Blythe D.;Singh, Akhilesh K.;Khim, Socheath;Mucci, Juan;Liggitt, Denny;Campetella, Oscar;Oukka, Mohamed;Gruppi, Adriana;Rawlings, David J.
通讯作者：
Rawlings, David J.
影响因子：
3.1
作者：
Hoft, DF;Schnapp, AR;Roodman, ST
通讯作者：
Roodman, ST
DOI：
10.1164/rccm.201304-0803oc
发表时间：
2013-11-01
影响因子：
24.7
作者：
Gopal, Radha;Monin, Leticia;Khader, Shabaana A.
通讯作者：
Khader, Shabaana A.
影响因子：
4.2
作者：
Machado, Alexandre V.;Cardoso, Jarbas E.;Bruna-Romero, Oscar
通讯作者：
Bruna-Romero, Oscar
影响因子：
4.8
作者：
Huppert, Jula;Closhen, Dorothea;Kuhlmann, Christoph R. W.
通讯作者：
Kuhlmann, Christoph R. W.