University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Microbiology and Physiological Systems

Publication Date

12-21-2017

Document Type

Article Preprint

Disciplines

Bacterial Infections and Mycoses | Immunology of Infectious Disease | Medical Immunology | Microbiology

Abstract

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.

Keywords

phagocyte, oxidase, tuberculosis, NADPH, superoxides, mice, Caspase1, immunology

Rights and Permissions

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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

10.1101/232777

Source

bioRxiv 232777; doi: https://doi.org/10.1101/232777. Link to preprint on bioRxiv service.

Journal/Book/Conference Title

bioRxiv

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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