The Phagocyte Oxidase Controls Tolerance to Mycobacterium tuberculosis Infection.

Journal Article (Journal Article)

Protection from infectious disease relies on two distinct strategies: antimicrobial resistance directly inhibits pathogen growth, whereas infection tolerance protects from the negative impact of infection on host health. A single immune mediator can differentially contribute to these strategies in distinct contexts, confounding our understanding of protection to different pathogens. For example, the NADPH-dependent phagocyte oxidase (Phox) complex produces antimicrobial superoxide and protects from tuberculosis (TB) in humans. However, Phox-deficient mice display no sustained resistance defects to Mycobacterium tuberculosis, suggesting a more complicated role for NADPH Phox complex than strictly controlling bacterial growth. We examined the mechanisms by which Phox contributes to protection from TB and found that mice lacking the Cybb subunit of Phox suffered from a specific defect in tolerance, which was caused by unregulated Caspase-1 activation, IL-1β production, and neutrophil influx into the lung. These studies imply that a defect in tolerance alone is sufficient to compromise immunity to M. tuberculosis and highlight a central role for Phox and Caspase-1 in regulating TB disease progression.

Full Text

Duke Authors

Cited Authors

  • Olive, AJ; Smith, CM; Kiritsy, MC; Sassetti, CM

Published Date

  • September 15, 2018

Published In

Volume / Issue

  • 201 / 6

Start / End Page

  • 1705 - 1716

PubMed ID

  • 30061198

Pubmed Central ID

  • PMC6125170

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1800202


  • eng

Conference Location

  • United States