Dynamics of Th17 cells and their role in Schistosoma japonicum infection in C57BL/6 mice.
Dynamics of Th17 cells and their role in Schistosoma japonicum infection in C57BL/6 mice.
复制标题
Th17 细胞动态及其在 C57BL/6 小鼠日本血吸虫感染中的作用
DOI：
10.1371/journal.pntd.0001399
复制
发表时间：
2011-11
影响因子：
3.8
通讯作者：
Su C
中科院分区：
文献类型：
--
作者：
Wen X;He L;Chi Y;Zhou S;Hoellwarth J;Zhang C;Zhu J;Wu C;Dhesi S;Wang X;Liu F;Su C
血吸虫病是一种主要的热带寄生虫病，目前关于血吸虫病免疫应答的知识还不充分，更好地了解这些应答将有助于开发疫苗或治疗方法来控制肉芽肿相关的免疫病理。CD4+ T细胞在宿主抗寄生虫感染的免疫应答和血吸虫病的免疫病理中都起着关键作用。T辅助性（th1）、Th2和T调节性（Treg）细胞的诱导及其在血吸虫感染中的作用得到了很好的阐释。然而，关于日本血吸虫感染后Th17细胞（另一个重要的CD4+ T细胞亚群）的动态，以及这些细胞及其决定性的IL-17细胞因子是否在感染早期介导宿主保护反应的体内数据很少。方法观察日本血吸虫感染不同阶段Th17和其他3种CD4+ T细胞亚群的水平以及诱导或抑制Th17细胞生成的相关细胞因子。与体外研究报道相反，我们的研究结果表明，在日本血吸虫感染小鼠中，Th17细胞与Th1、Th2、Treg细胞以及IFN-γ和IL-4细胞因子一起被诱导。结果还表明，日本血吸虫卵抗原优先诱导Th17细胞的产生，而成虫抗原不优先诱导Th17细胞的产生。此外，用中和性抗IL-17单克隆抗体（mAb）降低IL-17可提高小鼠的血吸虫特异性抗体水平和对日本血吸虫感染的部分保护作用。结论本研究首次报道了日本血吸虫感染过程中Th17细胞的动态变化，表明Th17细胞分化是血吸虫诱导因子和抑制因子共同作用的结果。重要的是，我们的研究结果表明，较低的IL-17水平可能导致有利的宿主保护反应。这项研究有助于了解血吸虫病的免疫，并可能有助于开发保护宿主免受感染或抑制免疫病理的干预措施。
Background The current knowledge of immunological responses to schistosomiasis, a major tropical helminthic disease, is insufficient, and a better understanding of these responses would support vaccine development or therapies to control granuloma-associated immunopathology. CD4+ T cells play critical roles in both host immune responses against parasitic infection and immunopathology in schistosomiasis. The induction of T helper (Th)1, Th2 and T regulatory (Treg) cells and their roles in schistosome infections are well-illustrated. However, little in vivo data are available on the dynamics of Th17 cells, another important CD4+ T cell subset, after Schistosoma japonicum infection or whether these cells and their defining IL-17 cytokine mediate host protective responses early in infection. Methodology Levels of Th17 and the other three CD4+ T cell subpopulations and the cytokines related to induction or repression of Th17 cell generation in different stages of S. japonicum infection were observed. Contrary to reported in vitro studies, our results showed that the Th17 cells were induced along with the Th1, Th2, Treg cells and the IFN-γ and IL-4 cytokines in S. japonicum infected mice. The results also suggested that S. japonicum egg antigens but not adult worm antigens preferentially induced Th17 cell generation. Furthermore, decreasing IL-17 with a neutralizing anti-IL-17 monoclonal antibody (mAb) increased schistosome-specific antibody levels and partial protection against S. japonicum infection in mice. Conclusions Our study is the first to report the dynamics of Th17 cells during S. japonicum infection and indicate that Th17 cell differentiation results from the integrated impact of inducing and suppressive factors promoted by the parasite. Importantly, our findings suggest that lower IL-17 levels may result in favorable host protective responses. This study significantly contributes to the understanding of immunity to schistosomiasis and may aid in developing interventions to protect hosts from infection or restrain immunopathology.
登录
查看更多内容
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
3.1
作者：
de Almeida, AB;Silva, MCME;Freedman, DO
通讯作者：
Freedman, DO
白介素（IL）-10在愈合后皮肤中持续的持久性以及抗IL-10受体抗体对无菌治疗的治疗潜力的作用。
DOI：
10.1084/jem.194.10.1497
发表时间：
2001-11-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Belkaid Y;Hoffmann KF;Mendez S;Kamhawi S;Udey MC;Wynn TA;Sacks DL
通讯作者：
Sacks DL
影响因子：
4.4
作者：
Chung, DR;Kasper, DL;Tzianabos, AO
通讯作者：
Tzianabos, AO