Department of Microbiology and Physiological Systems
Bacterial Infections and Mycoses | Immunology of Infectious Disease | Medical Immunology | Microbiology
Protection from infectious disease relies on two distinct mechanisms. 'Antimicrobial resistance' directly inhibits pathogen growth, whereas 'infection tolerance' controls tissue damage. A single immune-mediator can differentially contribute to these mechanisms in distinct contexts, confounding our understanding of protection to different pathogens. For example, the NADPH-dependent phagocyte oxidase complex (Phox) produces anti-microbial superoxides and protects from tuberculosis in humans. However, Phox-deficient mice do not display the expected defect in resistance to M. tuberculosis leaving the role of this complex unclear. We re-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 due to unregulated Caspase1 activation, IL-1β production, and neutrophil influx into the lung. These studies demonstrate that Phox-derived superoxide protect against TB by promoting tolerance to persistent infection, and highlight a central role for Caspase1 in regulating TB disease progression.
phagocyte, oxidase, tuberculosis, NADPH, superoxides, mice, Caspase1, immunology
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY 4.0 International license.
DOI of Published Version
bioRxiv 232777; doi: https://doi.org/10.1101/232777. Link to preprint on bioRxiv service.
Olive AJ, Smith CM, Kiritsy MC, Sassetti CM. (2017). The Phagocyte Oxidase Controls Tolerance to Mycobacterium tuberculosis infection.. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/232777. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1517
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