Targeting immunometabolism in host defence against Mycobacterium tuberculosis

Immunology. 2021 Feb;162(2):145-159. doi: 10.1111/imm.13276. Epub 2020 Oct 28.


In the face of ineffective vaccines, increasing antibiotic resistance and the decline in new antibacterial drugs in the pipeline, tuberculosis (TB) still remains pandemic. Exposure to Mycobacterium tuberculosis (Mtb), which causes TB, results in either direct elimination of the pathogen, most likely by the innate immune system, or infection and containment that requires both innate and adaptive immunity to form the granuloma. Host defence strategies against infectious diseases are comprised of both host resistance, which is the ability of the host to prevent invasion or to eliminate the pathogen, and disease tolerance, which is defined by limiting the collateral tissue damage. In this review, we aim to examine the metabolic demands of the immune cells involved in both host resistance and disease tolerance, chiefly the macrophage and T-lymphocyte. We will further discuss how baseline metabolic heterogeneity and inflammation-driven metabolic reprogramming during infection are linked to their key immune functions containing mycobacterial growth and instructing protective immunity. Targeting key players in immune cellular metabolism may provide a novel opportunity for treatments at different stages of TB disease.

Keywords: Mycobacterium tuberculosis; ATP; T-cell; Trained immunity; alveolar macrophage; disease tolerance; fatty acid oxidation; glycolysis; host resistance; immunometabolism; lymphocyte; macrophage; metabolism; oxidative phosphorylation; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immune Tolerance / immunology
  • Immunity, Innate / immunology
  • Inflammation / immunology
  • Inflammation / microbiology
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology