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Regulation of mycobacterial infection by macrophage Gch1 and tetrahydrobiopterin

Abstract:

Inducible nitric oxide synthase (iNOS) plays a crucial role in controlling growth of Mycobacterium tuberculosis (M.tb), presumably via nitric oxide (NO) mediated killing. Here we show that leukocyte-specific deficiency of NO production, through targeted loss of the iNOS cofactor tetrahydrobiopterin (BH4), results in enhanced control of M.tb infection; by contrast, loss of iNOS renders mice susceptible to M.tb. By comparing two complementary NO-deficient models, Nos2-/-mice and BH4 deficien...

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Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-018-07714-9

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Cardiovascular Medicine
Role:
Author
ORCID:
0000-0003-0971-9858
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM
Sub department:
Jenner Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM
Sub department:
RDM Cardiovascular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM
Sub department:
Jenner Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM
Sub department:
RDM Cardiovascular Medicine
Role:
Author
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Oxford University Medical Research Fund More from this funder
John Fell Fund More from this funder
National Institute for Health Research More from this funder
Publisher:
Springer Nature Publisher's website
Journal:
Nature Communications Journal website
Volume:
9
Article number:
5409
Publication date:
2018-12-20
Acceptance date:
2018-11-21
DOI:
EISSN:
2041-1723
Pubs id:
pubs:944838
UUID:
uuid:f1bb7a8b-4b81-4223-bf96-14413e1080be
Local pid:
pubs:944838
Deposit date:
2018-11-21

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