Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis
Authors
Mishra, Bibhuti B.Lovewell, Rustin R.
Olive, Andrew J.
Smith, Clare M.
Phuah, Jia Yao
Long, Jarukit E.
Dubuke, Michelle L.
Palace, Samantha G.
Goguen, Jon D.
Baker, Richard E.
Nambi, Subhalaxmi
Mishra, Rabinarayan
Booty, Matthew G.
Baer, Christina E.
Shaffer, Scott A.
McCormick, Beth A.
Sassetti, Christopher M.
UMass Chan Affiliations
UMass Metabolic NetworkDepartment of Pathology
Proteomics and Mass Spectrometry Facility, Department of Biochemistry and Molecular Pharmacology
Department of Microbiology and Physiological Systems
Document Type
Journal ArticlePublication Date
2017-05-15Keywords
Antimicrobial responsesBacterial host response
Bacterial pathogenesis
Tuberculosis
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Microbiology
Molecular Biology
Metadata
Show full item recordAbstract
Nitric oxide contributes to protection from tuberculosis. It is generally assumed that this protection is due to direct inhibition of Mycobacterium tuberculosis growth, which prevents subsequent pathological inflammation. In contrast, we report that nitric oxide primarily protects mice by repressing an interleukin-1- and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes bacterial replication. Using M. tuberculosis mutants as indicators of the pathogen's environment, we inferred that granulocytic inflammation generates a nutrient-replete niche that supports M. tuberculosis growth. Parallel clinical studies indicate that a similar inflammatory pathway promotes tuberculosis in patients. The human 12/15-lipoxygenase orthologue, ALOX12, is expressed in cavitary tuberculosis lesions; the abundance of its products correlates with the number of airway neutrophils and bacterial burden and a genetic polymorphism that increases ALOX12 expression is associated with tuberculosis risk. These data suggest that M. tuberculosis exploits neutrophilic inflammation to preferentially replicate at sites of tissue damage that promote contagion.Source
Nat Microbiol. 2017 May 15;2:17072. doi: 10.1038/nmicrobiol.2017.72. Link to article on publisher's siteDOI
10.1038/nmicrobiol.2017.72Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36594PubMed ID
28504669Notes
Full author list omitted for brevity. For the full list of authors, see article.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/nmicrobiol.2017.72