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Exercise Activates Interferon Immune Response of the Liver via Gpld1 to Enhance Antiviral Innate Immunity

ABSTRACT:

Healthy behavioral patterns could modulate organ functions to enhance the body’s immunity. However, whether exercise regulates antiviral innate immunity remains elusive. Here, we found that exercise promotes type-I IFN (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could regulate IFN-I production, we identified Gpld1 as a crucial molecule and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1-/- mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction and therefore enhances IRF3 activation and IFN-I production, and improves the body’s antiviral ability. This study reveals that the exercise behavior improves antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity, and uncovers an unknown function of liver cells in innate immunity.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Tengfei Ren

PROVIDER: MTBLS7972 | MetaboLights | 2024-04-24

REPOSITORIES: MetaboLights

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