ABSTRACT

Innate immune signaling and xenophagy are crucial innate defense strategies exploited by the host to counteract intracellular pathogens with ubiquitination as a critical regulator of these processes. These pathogens, including Mycobacterium tuberculosis (M. tb), co-opt the host ubiquitin machinery by utilizing secreted or cell surface effectors to dampen innate host defenses. Inversely, the host utilizes ubiquitin ligase-mediated ubiquitination of intracellular pathogens and recruits autophagy receptors to induce xenophagy. In the current article, we discuss the co-option of the ubiquitin pathway by the M. tb virulence effectors.

Abbreviations: ANAPC2: anaphase promoting complex subunit 2; IL: interleukin; Lys: lysine (K); MAPK: mitogen-activated protein kinase; MAP3K7/TAK1; mitogen-activated protein kinase kinase kinase 7; M. tb: Mycobacterium tuberculosis; NFKB/NF-κB: nuclear factor kappa B subunit; PtpA: protein tyrosine phosphatase; SQSTM1/p62: sequestosome 1; V-ATPase: vacuolar-type H+-ATPase; UBA: a eukaryotic-like ubiquitin-associated domain

摘要

先天免疫信号和异体吞噬是宿主利用的关键先天防御策略，以通过泛素化作为这些过程的关键调节剂来对抗细胞内病原体。这些病原体，包括结核分枝杆菌( M. tb )，通过利用分泌的或细胞表面效应物来抑制先天宿主防御，从而共同选择宿主泛素机制。相反，宿主利用泛素连接酶介导的细胞内病原体泛素化并招募自噬受体来诱导异体自噬。在当前的文章中，我们讨论了M. tb毒力效应器对泛素途径的共同选择。

缩写：ANAPC2：后期促进复合亚基2；IL：白细胞介素；Lys：赖氨酸（K）；MAPK：丝裂原活化蛋白激酶；MAP3K7/TAK1；丝裂原活化蛋白激酶激酶激酶 7；M. tb：结核分枝杆菌；NFKB/NF-κB：核因子κB亚基；PtpA：蛋白酪氨酸磷酸酶；SQSTM1/p62：sequestosome 1；V-ATPase：液泡型H+-ATPase；UBA：真核样泛素相关域