Tuberculosis and the art of macrophage manipulation

Pathog Dis. 2018 Jun 1;76(4):fty037. doi: 10.1093/femspd/fty037.

Abstract

Macrophages are first-line responders against microbes. The success of Mycobacterium tuberculosis (Mtb) rests upon its ability to convert these antimicrobial cells into a permissive cellular niche. This is a remarkable accomplishment, as the antimicrobial arsenal of macrophages is extensive. Normally bacteria are delivered to an acidic, degradative lysosome through one of several trafficking pathways, including LC3-associated phagocytosis (LAP) and autophagy. Once phagocytozed, the bacilli are subjected to reactive oxygen and nitrogen species, and they induce the expression of proinflammatory cytokines, which serve to augment host responses. However, Mtb hijacks these host defense mechanisms, manipulating host cellular trafficking, innate immune responses, and cell death pathways to its benefit. The complex series of measures and countermeasures between host and pathogen ultimately determines the outcome of infection. In this review, we focus on the diverse effectors that Mtb uses in its multipronged effort to subvert the innate immune responses of macrophages. We highlight recent advances in understanding the molecular interface of the Mtb-macrophage interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Autophagy
  • Gene Expression Regulation
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunity, Innate
  • Lysosomes / immunology*
  • Lysosomes / microbiology
  • Macrophages / immunology*
  • Macrophages / microbiology
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / immunology
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity*
  • Phagocytosis
  • Signal Transduction
  • Tuberculosis / immunology*
  • Tuberculosis / metabolism
  • Tuberculosis / microbiology
  • Type VII Secretion Systems / genetics
  • Type VII Secretion Systems / immunology

Substances

  • Microtubule-Associated Proteins
  • Type VII Secretion Systems
  • light chain 3, human