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An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection.
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.
Type
Journal articleSubject
Alcohol OxidoreductasesAmino Acid Sequence
Animals
Humans
Inflammation
Leukotriene B4
Molecular Sequence Data
Mycobacterium Infections
Receptors, Leukotriene B4
Sequence Alignment
Tuberculosis
Zebrafish
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https://hdl.handle.net/10161/11197Published Version (Please cite this version)
10.1371/journal.pone.0067828Publication Info
(2013). An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial
infection. PLoS One, 8(7). pp. e67828. 10.1371/journal.pone.0067828. Retrieved from https://hdl.handle.net/10161/11197.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Dennis Ko
Associate Professor in Molecular Genetics and Microbiology
Using Pathogens to Decipher Genetic Variation Connecting Cell Biology and Disease
SusceptibilityDespite improvements in public health, advancements in vaccines, and
the development of many classes of antibiotics, infectious disease is still responsible
for over a quarter of all deaths worldwide. However, even for the most devastating
of pandemics, individuals demonstrate a large variability in the severity of infection.
The long-term goal of the lab is to understand the ge
David M. Tobin
Professor of Molecular Genetics and Microbiology
Tuberculosis: Mycobacterial Pathogenesis and Host Susceptibility
Tuberculosis kills 1.5 million people annually. Our laboratory aims to understand
the intricate interplay between mycobacteria and their hosts using a combination of
model organism genetics, human genetics, pharmacology and high-resolution microscopy.
By identifying key pathways utilized by the infecting bacteria and the host innate
immune system, we hope to discover new therapeutic targets and interventi
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