DUSP5 (dual-specificity protein phosphatase 5) suppresses BCG-induced autophagy via ERK 1/2 signaling pathway. (October 2020)

• Record Type: Journal Article
• Authors: Luo, Jia; Xue, Di; Song, Fuyang; Liu, Xiaoming; Li, Wu; Wang, Yujiong
• Is Part Of: Molecular immunology. Volume 126(2020:Oct.)
• Page Start: 101
• Page End: 109
• Publication Date: 2020-10
• Subjects: Dual specificity phosphatase 5 -- Autophagy -- Bacillus calmette-guerin -- ERK1/2 signaling pathway -- Macrophage; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.07.019
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: BCG infection induces DUSP5 expression. BCG infection activates ERK1/2 signaling. DUSP5 knockdown increases the expression of autophagy-related proteins. DUSP5 suppresses BCG induced autophagy. Abstract: 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.