Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China.
Department of Gastroenterology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Int Immunopharmacol. 2022 Jul;108:108742. doi: 10.1016/j.intimp.2022.108742. Epub 2022 Apr 1.
Interleukin-33 (IL-33) is a member of the interleukin-1 family, which is reported to be important across a range of diseases. However, the mechanisms underlying IL-33/ST2 axis in infectious diseases have not yet been fully addressed.
We established both lipopolysaccharide (LPS)-induced injuryin T cells and Listeria monocytogenes (Lm) infection model to determine the effect of IL-33 on infectious immunity.
The T cell proliferation was inhibited by LPS while IL-33 could reverse the outcome. Further, apoptosis was significantly promoted after serum stimulation (ST)2 knockdown, suggesting IL-33, acting through its receptor ST2, may attenuate the inhibitory effect of LPS on T cells through the apoptotic signaling pathway. In this study, we also identified an IL-33-mediated mechanism of T cell differentiation in pregnant mice infected with Lm. Here, we observed the elevated expression of IL-33 in pregnant mice infected with Lm. Furthermore, we revealed that blocking IL-33 markedly decreased the abortion rate and placental bacterial load, but weakened placental inflammatory repair, by inhibiting Th2 cell-mediated immune responses and relatively intensifying Th1-dominent immunoreaction.
These findings reveal a previously unidentified mechanism underlying IL-33/ST2 axis. IL-33 signaling and targeting T cell-mediated immunity may present a new therapeutic strategy for the treatment of infectious diseases.
白细胞介素-33（IL-33）是白细胞介素-1 家族的成员，据报道在多种疾病中具有重要作用。然而，IL-33/ST2 轴在传染病中的作用机制尚未得到充分阐明。
我们建立了脂多糖（LPS）诱导的 T 细胞损伤和李斯特菌（Lm）感染模型，以确定 IL-33 对感染免疫的影响。
LPS 可抑制 T 细胞增殖，而 IL-33 可逆转这种结果。此外，ST2 敲低后血清刺激明显促进了细胞凋亡，表明 IL-33 通过其受体 ST2 作用可能通过凋亡信号通路减轻 LPS 对 T 细胞的抑制作用。在这项研究中，我们还鉴定了 IL-33 在感染李斯特菌的妊娠小鼠中调节 T 细胞分化的机制。在这里，我们观察到感染 Lm 的妊娠小鼠中 IL-33 的表达升高。此外，我们发现阻断 IL-33 可显著降低流产率和胎盘细菌负荷，但通过抑制 Th2 细胞介导的免疫反应和相对增强 Th1 优势免疫反应，削弱了胎盘炎症修复。
这些发现揭示了 IL-33/ST2 轴的一个以前未被识别的机制。IL-33 信号和靶向 T 细胞介导的免疫可能为治疗传染病提供一种新的治疗策略。
