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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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. [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/232777. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1517
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This work is licensed under a Creative Commons Attribution 4.0 License.