The phytochemical bergenin as an adjunct immunotherapy for tuberculosis in mice.
J Biol Chem
; 294(21): 8555-8563, 2019 05 24.
Article
en En
| MEDLINE
| ID: mdl-30975902
The widespread availability and use of modern synthetic therapeutic agents have led to a massive decline in ethnomedical therapies. However, these synthetic agents often possess toxicity leading to various adverse effects. For instance, anti-tubercular treatment (ATT) is toxic, lengthy, and severely impairs host immunity, resulting in posttreatment vulnerability to reinfection and reactivation of tuberculosis (TB). Incomplete ATT enhances the risk for the generation of multidrug- or extensively drug-resistant (MDR or XDR, respectively) variants of Mycobacterium tuberculosis (M. tb), the TB-causing microbe. Therefore, a new therapeutic approach that minimizes these risks is urgently needed to combat this deadly disease and prevent future TB epidemics. Previously, we have shown that the phytochemical bergenin induces T helper 1 (Th1)- and Th17 cell-based protective immune responses and potently inhibits mycobacterial growth in a murine model of M. tb infection, suggesting bergenin as a potential adjunct agent to TB therapy. Here, we combined ATT therapy with bergenin and found that this combination reduces immune impairment and the length of treatment in mice. We observed that co-treatment with the anti-TB drug isoniazid and bergenin produces additive effects and significantly reduces bacterial loads compared with isoniazid treatment alone. The bergenin co-treatment also reduced isoniazid-induced immune impairment; promoted long-lasting, antigen-specific central memory T cell responses; and acted as a self-propelled vaccine. Of note, bergenin treatment significantly reduced the bacterial burden of a multidrug-resistant TB strain. These observations suggest that bergenin is a potent immunomodulatory agent that could be further explored as a potential adjunct to TB therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benzopiranos
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Tuberculosis Resistente a Múltiples Medicamentos
/
Células TH1
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Farmacorresistencia Bacteriana Múltiple
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Células Th17
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Inmunoterapia
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Isoniazida
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Mycobacterium tuberculosis
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Estados Unidos