TNF-α antagonists differentially induce TGF-ß1-dependent resuscitation of dormant-like Mycobacterium tuberculosis.
PLoS Pathog
; 16(2): e1008312, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-32069329
ABSTRACT
TNF-α- as well as non-TNF-α-targeting biologics are prescribed to treat a variety of immune-mediated inflammatory disorders. The well-documented risk of tuberculosis progression associated with anti-TNF-α treatment highlighted the central role of TNF-α for the maintenance of protective immunity, although the rate of tuberculosis detected among patients varies with the nature of the drug. Using a human, in-vitro granuloma model, we reproduce the increased reactivation rate of tuberculosis following exposure to Adalimumab compared to Etanercept, two TNF-α-neutralizing biologics. We show that Adalimumab, because of its bivalence, specifically induces TGF-ß1-dependent Mycobacterium tuberculosis (Mtb) resuscitation which can be prevented by concomitant TGF-ß1 neutralization. Moreover, our data suggest an additional role of lymphotoxin-α-neutralized by Etanercept but not Adalimumab-in the control of latent tuberculosis infection. Furthermore, we show that, while Secukinumab, an anti-IL-17A antibody, does not revert Mtb dormancy, the anti-IL-12-p40 antibody Ustekinumab and the recombinant IL-1RA Anakinra promote Mtb resuscitation, in line with the importance of these pathways in tuberculosis immunity.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Tuberculosis
/
Inhibidores del Factor de Necrosis Tumoral
/
Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suiza