EspR promotes mycobacteria survival in macrophages by inhibiting MyD88 mediated inflammation and apoptosis

Tuberculosis (Edinb). 2019 May;116:22-31. doi: 10.1016/ Epub 2019 Apr 4.


Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), leading to about a million deaths each year. EspR is a DNA binding protein of Mtb which regulates expression of multiple genes and the activity of ESX-1 secretion system of the bacteria, with itself being secreted out as a substrate of ESX-1. We explored the function of secreted EspR in host cells by overexpressing the protein in murine macrophage cell line RAW264.7, infecting the cells with BCG which does not secrete EspR, and evaluating the antimicrobial responses of the cells. We found that EspR resulted in an increased intracellular bacteria load in macrophages. This is due to its inhibition on BCG induced expression of inflammatory cytokines and inducible nitric oxide synthase (iNOS), as well as host cell apoptosis. Mechanism study showed that EspR directly interacted with adaptor protein myeloid differentiation factor 88 (MyD88), suppressed MyD88 dependent Toll-like receptor (TLR) and IL-1R signal activation, thus reduced inflammatory responses and apoptosis in macrophages and promoted mycobacteria survival.

Keywords: EspR; Inflammation; Macrophage; MyD88; Toll-like receptor; Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / metabolism
  • Apoptosis*
  • Bacterial Load
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • HEK293 Cells
  • Host-Pathogen Interactions
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / microbiology*
  • Inflammation / pathology
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / microbiology*
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbial Viability
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / metabolism*
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • RAW 264.7 Cells
  • Signal Transduction


  • Antigens, Bacterial
  • Bacterial Proteins
  • ESAT-6 protein, Mycobacterium tuberculosis
  • IL1B protein, mouse
  • Inflammation Mediators
  • Interleukin-1beta
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse