The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310051, P. R. China.
Departement of Pediatrics, Red Cross Hospital of Hangzhou, Hangzhou, 310003, P. R. China.
Sci Rep. 2017 Oct 17;7(1):13319. doi: 10.1038/s41598-017-13825-y.
Excessive immune responses played an important role in pathophysiology of mycoplasma pneumonia (MP) infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a negative regulator of immune response. This study investigated the expression change of TIPE2 and its role in immune defense against MP infection, as well as the underlying mechanisms. Expressions of TIPE2 both in patients and in macrophages in vitro after MP infection were measured. We further studied cytokine production and mitogen-activated protein kinase (MAPK) signaling function in macrophages with interfered expression of TIPE2 upon MP infection. A significant decrease of TIPE2 mRNA expression was observed in peripheral blood mononuclear cells (PBMCs) from MP patients, which was correlated with the severity of infection. Accordingly we found down-regulation of TIPE2 expression in macrophages after MP infection. In vitro study further suggested that TIPE2 jeopardized inflammatory cytokine production trigged by MP infection via inhibiting MAPK signaling pathway. These findings provided evidences of the novel function of TIPE2 in anti-MP immunity and its possible clinical utility related clinical significance.
过度的免疫反应在肺炎支原体 (MP) 感染的病理生理学中起着重要作用。肿瘤坏死因子-α诱导蛋白 8 样蛋白 2 (TIPE2) 是免疫反应的负调节剂。本研究旨在探讨 TIPE2 的表达变化及其在抗 MP 感染免疫防御中的作用及其潜在机制。检测了 MP 感染后患者和体外巨噬细胞中 TIPE2 的表达变化。我们进一步研究了在 MP 感染时干扰 TIPE2 表达后巨噬细胞中细胞因子产生和丝裂原活化蛋白激酶 (MAPK) 信号转导功能。从 MP 患者的外周血单核细胞 (PBMC) 中观察到 TIPE2mRNA 表达显著降低,这与感染的严重程度相关。相应地,我们发现 MP 感染后巨噬细胞中 TIPE2 的表达下调。体外研究进一步表明,TIPE2 通过抑制 MAPK 信号通路,危及 MP 感染引发的炎症细胞因子产生。这些发现为 TIPE2 在抗 MP 免疫中的新功能及其可能的临床意义提供了证据。