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TGF-?1 Suppresses the Type I IFN Response and Induces Mitochondrial Dysfunction in Alveolar Macrophages.

ABSTRACT: TGF-?1 is a pleiotropic cytokine with an established role in fibrosis; however, the immunosuppressive effects of TGF-?1 are less characterized. Elevated levels of TGF-?1 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-?1 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-?1 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-?1 treatment further exacerbated mitochondrial dysfunction. The TGF-?1 and TGF-?1+RSV-treated macrophages had a higher frequency of apoptosis and diminished phagocytic capacity, potentially through mitochondrial stress. Disruption of TGF-?1 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.

SUBMITTER: Grunwell JR

PROVIDER: S-EPMC5928790 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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TGF-β1 Suppresses the Type I IFN Response and Induces Mitochondrial Dysfunction in Alveolar Macrophages.

Grunwell Jocelyn R JR Yeligar Samantha M SM Stephenson Susan S Ping Xiao Du XD Gauthier Theresa W TW Fitzpatrick Anne M AM Brown Lou Ann S LAS

Journal of immunology (Baltimore, Md. : 1950) 20180202 6

TGF-β1 is a pleiotropic cytokine with an established role in fibrosis; however, the immunosuppressive effects of TGF-β1 are less characterized. Elevated levels of TGF-β1 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 a ...[more]

PMID: 29427413

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Dataset Information

TGF-?1 Suppresses the Type I IFN Response and Induces Mitochondrial Dysfunction in Alveolar Macrophages.

Publications

TGF-β1 Suppresses the Type I IFN Response and Induces Mitochondrial Dysfunction in Alveolar Macrophages.

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