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Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.

Publication ,  Journal Article
Mishra, BB; Lovewell, RR; Olive, AJ; Zhang, G; Wang, W; Eugenin, E; Smith, CM; Phuah, JY; Long, JE; Dubuke, ML; Palace, SG; Goguen, JD ...
Published in: Nat Microbiol
May 15, 2017

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.

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Published In

Nat Microbiol

DOI

EISSN

2058-5276

Publication Date

May 15, 2017

Volume

2

Start / End Page

17072

Location

England

Related Subject Headings

  • Tuberculosis
  • Nitric Oxide
  • Neutrophils
  • Mycobacterium tuberculosis
  • Mice, Inbred C57BL
  • Interleukin-1
  • Inflammation
  • Humans
  • Down-Regulation
  • Disease Models, Animal
 

Citation

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Mishra, B. B., Lovewell, R. R., Olive, A. J., Zhang, G., Wang, W., Eugenin, E., … Sassetti, C. M. (2017). Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. Nat Microbiol, 2, 17072. https://doi.org/10.1038/nmicrobiol.2017.72
Mishra, Bibhuti B., Rustin R. Lovewell, Andrew J. Olive, Guoliang Zhang, Wenfei Wang, Eliseo Eugenin, Clare M. Smith, et al. “Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.Nat Microbiol 2 (May 15, 2017): 17072. https://doi.org/10.1038/nmicrobiol.2017.72.
Mishra BB, Lovewell RR, Olive AJ, Zhang G, Wang W, Eugenin E, et al. Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. Nat Microbiol. 2017 May 15;2:17072.
Mishra, Bibhuti B., et al. “Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.Nat Microbiol, vol. 2, May 2017, p. 17072. Pubmed, doi:10.1038/nmicrobiol.2017.72.
Mishra BB, Lovewell RR, Olive AJ, Zhang G, Wang W, Eugenin E, Smith CM, Phuah JY, Long JE, Dubuke ML, Palace SG, Goguen JD, Baker RE, Nambi S, Mishra R, Booty MG, Baer CE, Shaffer SA, Dartois V, McCormick BA, Chen X, Sassetti CM. Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. Nat Microbiol. 2017 May 15;2:17072.

Published In

Nat Microbiol

DOI

EISSN

2058-5276

Publication Date

May 15, 2017

Volume

2

Start / End Page

17072

Location

England

Related Subject Headings

  • Tuberculosis
  • Nitric Oxide
  • Neutrophils
  • Mycobacterium tuberculosis
  • Mice, Inbred C57BL
  • Interleukin-1
  • Inflammation
  • Humans
  • Down-Regulation
  • Disease Models, Animal