Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan, Ningxia 750021, China; School of Life Sciences, Ningxia University, Yinchuan, Ningxia 750021, China.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan, Ningxia 750021, China; School of Life Sciences, Ningxia University, Yinchuan, Ningxia 750021, China.
Mol Immunol. 2020 Oct;126:101-109. doi: 10.1016/j.molimm.2020.07.019. Epub 2020 Aug 11.
Autophagy is considered as an effective strategy for host cells to eliminate intracellular Mycobacterium tuberculosis (Mtb). Dual-specificity phosphatase 5 (DUSP5) is an endogenous phosphatase of ERK1/2, and plays an important role in host innate immune responses, its function in autophagy regulation however remains unexplored. In the present study, the function of DUSP5 in autophagy in Mycobacterium bovis Bacillus Calmette-Guerin (BCG)-infected RAW264.7 cells, a murine macrophage-like cell line, was examined by assessing the alteration of the cell morphology, expression of autophagy markers, and ERK1/2 signaling activation. The results demonstrated that the BCG infection could induce DUSP5 expression and activate ERK1/2 signaling in RAW264.7 cells; an activation of ERK1/2 signaling contributed to autophagic process in RAW264.7 cells. Moreover, DUSP5 knockdown increased the expression of autophagy-related proteins (Atgs), including LC3-II, Beclin1, Atg5 and Atg7. However, an overexpression of DUSP5 exhibited an opposite effect. Mechanistically, DUSP5 could inhibit the formation of autophagosome by suppressing the phosphorylation of signaling molecules in ERK1/2 signaling cascade. This study thus demonstrated a novel role of DUSP5 in modulating autophagy inRAW264.7 cells in response to BCG infection in particular, and autophagy macrophage to Mtb in general.
自噬被认为是宿主细胞清除细胞内结核分枝杆菌（Mycobacterium tuberculosis，Mtb）的有效策略。双特异性磷酸酶 5（Dual-specificity phosphatase 5，DUSP5）是 ERK1/2 的内源性磷酸酶，在宿主固有免疫反应中发挥重要作用，但其在自噬调控中的作用尚不清楚。在本研究中，通过评估细胞形态的变化、自噬标记物的表达和 ERK1/2 信号转导的激活，检测了 DUSP5 在牛分枝杆菌卡介苗（Mycobacterium bovis Bacillus Calmette-Guerin，BCG）感染 RAW264.7 细胞（一种鼠源巨噬样细胞系）中自噬的功能。结果表明，BCG 感染可诱导 RAW264.7 细胞中 DUSP5 的表达和 ERK1/2 信号的激活；ERK1/2 信号的激活有助于 RAW264.7 细胞中的自噬过程。此外，DUSP5 敲低增加了自噬相关蛋白（Atgs）的表达，包括 LC3-II、Beclin1、Atg5 和 Atg7。然而，DUSP5 的过表达则表现出相反的效果。机制上，DUSP5 通过抑制 ERK1/2 信号级联中信号分子的磷酸化来抑制自噬体的形成。因此，本研究表明 DUSP5 在调节 RAW264.7 细胞对 BCG 感染的自噬中具有新的作用，特别是在巨噬细胞对 Mtb 的自噬中。
