Cotreatment With Clofazimine and Rapamycin Eliminates Drug-Resistant Tuberculosis by Inducing Polyfunctional Central Memory T-Cell Responses.
J Infect Dis
; 228(9): 1166-1178, 2023 11 02.
Article
en En
| MEDLINE
| ID: mdl-37290049
ABSTRACT
Mycobacterium tuberculosis, the causative agent of tuberculosis, is acquiring drug resistance at a faster rate than the discovery of new antibiotics. Therefore, alternate therapies that can limit the drug resistance and disease recurrence are urgently needed. Emerging evidence indicates that combined treatment with antibiotics and an immunomodulator provides superior treatment efficacy. Clofazimine (CFZ) enhances the generation of T central memory (TCM) cells by blocking the Kv1.3+ potassium channels. Rapamycin (RAPA) facilitates M. tuberculosis clearance by inducing autophagy. In this study, we observed that cotreatment with CFZ and RAPA potently eliminates both multiple and extensively drug-resistant (MDR and XDR) clinical isolates of M. tuberculosis in a mouse model by inducing robust T-cell memory and polyfunctional TCM responses. Furthermore, cotreatment reduces the expression of latency-associated genes of M. tuberculosis in human macrophages. Therefore, CFZ and RAPA cotherapy holds promise for treating patients infected with MDR and XDR strains of M. tuberculosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tuberculosis Resistente a Múltiples Medicamentos
/
Mycobacterium tuberculosis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Infect Dis
Año:
2023
Tipo del documento:
Article
País de afiliación:
India