Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection.
Animals
B-Lymphocytes
/ drug effects
Cell Aggregation
/ drug effects
Disease Models, Animal
Female
Lung
/ immunology
Mice
Moxifloxacin
/ pharmacology
Mycobacterium tuberculosis
/ drug effects
Necrosis
Neutrophil Infiltration
/ drug effects
Polymethacrylic Acids
/ pharmacology
Sirolimus
/ pharmacology
Tuberculosis
/ immunology
Host-directed therapy
Inflammation
Rapamycin
Tuberculosis
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
15
03
2021
accepted:
01
09
2021
pubmed:
7
9
2021
medline:
22
3
2022
entrez:
6
9
2021
Statut:
ppublish
Résumé
Tuberculosis (TB) treatment regimens are lengthy, causing non-adherence to treatment. Inadequate treatment can lead to relapse and the development of drug resistance TB. Furthermore, patients often exhibit residual lung damage even after cure, increasing the risk for relapse and development of other chronic respiratory illnesses. Host-directed therapeutics are emerging as an attractive means to augment the success of TB treatment. In this study, we used C3HeB/FeJ mice as an experimental model to investigate the potential role of rapamycin, a mammalian target of rapamycin inhibitor, as an adjunctive therapy candidate during the treatment of Mycobacterium tuberculosis infection with moxifloxacin. We report that administration of rapamycin with or without moxifloxacin reduced infection-induced lung inflammation, and the number and size of caseating necrotic granulomas. Results from this study strengthen the potential use of rapamycin and its analogs as adjunct TB therapy, and importantly underscore the utility of the C3HeB/FeJ mouse model as a preclinical tool for evaluating host-directed therapy candidates for the treatment of TB.
Identifiants
pubmed: 34486033
pii: 272048
doi: 10.1242/dmm.049018
pmc: PMC8560501
pii:
doi:
Substances chimiques
Polymethacrylic Acids
0
methylmethacrylate-methacrylic acid copolymer
25086-15-1
Moxifloxacin
U188XYD42P
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM121176
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI042999
Pays : United States
Organisme : NIAID NIH HHS
ID : UH2 AI122313
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111935
Pays : United States
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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