Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; and.
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; and
J Immunol. 2020 May 15;204(10):2754-2761. doi: 10.4049/jimmunol.2000046. Epub 2020 Apr 8.
colonizes at the colon and causes mucosal inflammation in mice. Previous studies have revealed the importance of the innate and adaptive immune response for controlling infection. In the present study, we examined the role of T follicular helper (Tfh) cells in intestinal infection using mice with deficiency in T cells. Tfh cells were absolutely required at the late, but not the early, phase to control infection. Compared with control mice, we observed systemic pathogen dissemination and more severe colitis in Tfh-deficient mice. Furthermore, the susceptibility of Tfh-deficient mice correlated with an impaired serum IgG1 response to infection, and serum Abs from infected wild-type mice protected Tfh-deficient mice from infection. The transfer of wild-type Tfh cells also restored the levels of IgG1 and led to effective clearance of the pathogens in Tfh-deficient mice. Moreover, during infection, IL-21- and IL-4-producing Tfh cells were increased obviously in wild-type mice, correlating with IgG1 as the major isotype in germinal center B cells. Taken together, our work highlights the requirement and the function of Tfh cells in regulating humoral response for the host protection against infection.
定植于结肠并在小鼠中引起黏膜炎症。先前的研究揭示了先天和适应性免疫反应对于控制感染的重要性。在本研究中,我们使用缺乏 T 细胞的小鼠研究了滤泡辅助性 T(Tfh)细胞在肠道感染中的作用。Tfh 细胞在晚期而非早期对于控制感染是绝对必需的。与对照小鼠相比,我们观察到 Tfh 缺陷型小鼠中存在全身病原体传播和更严重的结肠炎。此外,Tfh 缺陷型小鼠的易感性与感染后血清 IgG1 反应受损相关,并且来自感染野生型小鼠的血清 Abs 可保护 Tfh 缺陷型小鼠免受感染。野生型 Tfh 细胞的转移也恢复了 IgG1 的水平,并导致 Tfh 缺陷型小鼠中病原体的有效清除。此外,在感染期间,野生型小鼠中明显增加了产生 IL-21 和 IL-4 的 Tfh 细胞,与生发中心 B 细胞中 IgG1 作为主要同种型相关。总之,我们的工作强调了 Tfh 细胞在调节体液反应以宿主抵御感染中的必要性和功能。