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An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection.
Title | An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Tobin, DM, Roca, FJ, Ray, JP, Ko, DC, Ramakrishnan, L |
Journal | PLoS One |
Volume | 8 |
Issue | 7 |
Pagination | e67828 |
Date Published | 2013 |
ISSN | 1932-6203 |
Abstract | While tuberculosis susceptibility has historically been ascribed to failed inflammation, it is now known that an excess of leukotriene A4 hydrolase (LTA4H), which catalyzes the final step in leukotriene B4 (LTB4) synthesis, produces a hyperinflammatory state and tuberculosis susceptibility. Here we show that the LTB4-inactivating enzyme leukotriene B4 dehydrogenase/prostaglandin reductase 1 (LTB4DH/PTGR1) restricts inflammation and independently confers resistance to tuberculous infection. LTB4DH overexpression counters the susceptibility resulting from LTA4H excess while ltb4dh-deficient animals can be rescued pharmacologically by LTB4 receptor antagonists. These data place LTB4DH as a key modulator of TB susceptibility and suggest new tuberculosis therapeutic strategies. |
DOI | 10.1371/journal.pone.0067828 |
Alternate Journal | PLoS ONE |
PubMed ID | 23874453 |
PubMed Central ID | PMC3708926 |
Grant List | DP2 OD008614 / OD / NIH HHS / United States |