Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
Front Immunol. 2022 Feb 14;13:690667. doi: 10.3389/fimmu.2022.690667. eCollection 2022.
(Mtb) PPE36, a cell-wall-associated protein, is highly specific and conserved for the Mtb complex group. Although PPE36 has been proven essential for iron utilization, little is known about it in regulating host immune responses. Here we exhibited that PPE36 was preferentially enriched in Mtb virulent strains and could efficiently inhibit host inflammatory responses and increase bacterial loads in infected macrophages and mice. In exploring the underlying mechanisms, we found that PPE36 could robustly inhibit the activation of inflammatory NF-κB and MAPK (Erk, p38, and Jnk) pathways by promoting E3 ligase Smurf1-mediated ubiquitination and proteasomal degradation of MyD88 protein. Our research revealed a previously unknown function of PPE36 on modulating host immune responses and provided some clues to the development of novel tuberculosis treatment strategies based on immune regulation.
（Mtb）PPE36 是一种与细胞壁相关的蛋白，对结核分枝杆菌复合体群具有高度特异性和保守性。虽然已经证明 PPE36 对铁的利用是必不可少的，但对于它在调节宿主免疫反应方面的作用知之甚少。在这里，我们展示了 PPE36 优先富集在结核分枝杆菌毒力株中，并能够有效地抑制宿主炎症反应，增加感染巨噬细胞和小鼠中的细菌载量。在探索潜在机制时，我们发现 PPE36 可以通过促进 E3 连接酶 Smurf1 介导的 MyD88 蛋白泛素化和蛋白酶体降解，强力抑制炎症 NF-κB 和 MAPK（Erk、p38 和 Jnk）通路的激活。我们的研究揭示了 PPE36 在调节宿主免疫反应方面的一个以前未知的功能，并为基于免疫调节的新型结核病治疗策略的发展提供了一些线索。
