An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection.
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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Zebrafish
- Tuberculosis
- Sequence Alignment
- Receptors, Leukotriene B4
- Mycobacterium Infections
- Molecular Sequence Data
- Leukotriene B4
- Inflammation
- Humans
- General Science & Technology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Zebrafish
- Tuberculosis
- Sequence Alignment
- Receptors, Leukotriene B4
- Mycobacterium Infections
- Molecular Sequence Data
- Leukotriene B4
- Inflammation
- Humans
- General Science & Technology