Mycobacterium tuberculosis Mce3E suppresses host innate immune responses by targeting ERK1/2 signaling

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jie LiCui Hua Liu

Abstract

Crucial to the pathogenesis of the tuberculosis (TB)-causing pathogen Mycobacterium tuberculosis is its ability to subvert host immune defenses to promote its intracellular survival. The mammalian cell entry protein 3E (Mce3E), located in the region of difference 15 of the M. tuberculosis genome and absent in Mycobacterium bovis bacillus Calmette-Guérin, has an essential role in facilitating the internalization of mammalian cells by mycobacteria. However, relatively little is known about the role of Mce3E in modulation of host innate immune responses. In this study, we demonstrate that Mce3E inhibits the activation of the ERK1/2 signaling pathway, leading to the suppression of Tnf and Il6 expression, and the promotion of mycobacterial survival within macrophages. Mce3E interacts and colocalizes with ERK1/2 at the endoplasmic reticulum in a DEF motif (an ERK-docking motif)-dependent manner, relocates ERK1/2 from cytoplasm to the endoplasmic reticulum, and finally reduces the association of ERK1/2 with MEK1 and blocks the nuclear translocation of phospho-ERK1/2. A DEF motif mutant form of Mce3E (F294A) loses its ability to suppress Tnf and Il6 expression and to promote intracellular survival of mycobacteria. Inhibition of the ERK...Continue Reading

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Sep 18, 2015·Nature Chemical Biology·Reto Guler, Frank Brombacher
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Mar 28, 2021·Cellular & Molecular Immunology·Lihua QiangCui Hua Liu
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Aug 6, 2021·Molecular Biology Reports·Sadhana Sundararajan, Rajiniraja Muniyan

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