TGF-ß1 Suppresses the Type I IFN Response and Induces Mitochondrial Dysfunction in Alveolar Macrophages.
J Immunol
; 200(6): 2115-2128, 2018 03 15.
Article
en En
| MEDLINE
| ID: mdl-29427413
ABSTRACT
TGF-ß1 is a pleiotropic cytokine with an established role in fibrosis; however, the immunosuppressive effects of TGF-ß1 are less characterized. Elevated levels of TGF-ß1 are found in patients with acute and chronic lung diseases, and the underlying disease processes are exacerbated by respiratory viral infections. The alveolar macrophage is the first line of cellular defense against respiratory viral infections, and its response to infections is dependent on environmental cues. Using the mouse alveolar macrophage line, MH-S, and human CD14+ monocyte-derived macrophages, we examined the effects of TGF-ß1 on the type I IFN antiviral response, macrophage polarization, and mitochondrial bioenergetics following a challenge with human respiratory syncytial virus (RSV). Our results showed that TGF-ß1 treatment of macrophages decreased the antiviral and proinflammatory response, and suppressed basal, maximal, spare mitochondrial respiration, and mitochondrial ATP production. Challenge with RSV following TGF-ß1 treatment further exacerbated mitochondrial dysfunction. The TGF-ß1 and TGF-ß1+RSV-treated macrophages had a higher frequency of apoptosis and diminished phagocytic capacity, potentially through mitochondrial stress. Disruption of TGF-ß1 signaling or rescue of mitochondrial respiration may be novel therapeutically targetable pathways to improve macrophage function and prevent secondary bacterial infections that complicate viral respiratory infections.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Interferón Tipo I
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Macrófagos Alveolares
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Factor de Crecimiento Transformador beta1
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Mitocondrias
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Immunol
Año:
2018
Tipo del documento:
Article