β2-Adrenergic Receptor Enhances the Alternatively Activated Macrophages and Promotes Biliary Injuries Caused by Helminth Infection

Front Immunol. 2021 Oct 18:12:754208. doi: 10.3389/fimmu.2021.754208. eCollection 2021.

Abstract

The autonomic nervous system has been studied for its involvement in the control of macrophages; however, the mechanisms underlying the interaction between the adrenergic receptors and alternatively activated macrophages (M2) remain obscure. Using FVB wild-type and beta 2 adrenergic receptors knockout, we found that β2-AR deficiency alleviates hepatobiliary damage in mice infected with C. sinensis. Moreover, β2-AR-deficient mice decrease the activation and infiltration of M2 macrophages and decrease the production of type 2 cytokines, which are associated with a significant decrease in liver fibrosis in infected mice. Our in vitro results on bone marrow-derived macrophages revealed that macrophages from Adrb2-/- mice significantly decrease M2 markers and the phosphorylation of ERK/mTORC1 induced by IL-4 compared to that observed in M2 macrophages from Adrb2+/+ . This study provides a better understanding of the mechanisms by which the β2-AR enhances type 2 immune response through the ERK/mTORC1 signaling pathway in macrophages and their role in liver fibrosis.

Keywords: Clonorchis sinensis; ERK/mTORC1 signaling; beta 2 adrenergic receptor; liver fibrosis; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autonomic Nervous System / physiopathology
  • Bile Ducts / parasitology
  • Bile Ducts / pathology
  • Cells, Cultured
  • Clonorchiasis / complications*
  • Clonorchiasis / immunology
  • Clonorchiasis / physiopathology
  • Cytokines / blood
  • Humans
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / parasitology
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis, Biliary / etiology
  • Liver Cirrhosis, Biliary / immunology*
  • Liver Cirrhosis, Biliary / parasitology
  • Liver Cirrhosis, Biliary / pathology
  • MAP Kinase Signaling System
  • Macrophage Activation*
  • Macrophages / classification
  • Macrophages / immunology
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / physiology
  • Mice
  • Mice, Knockout
  • Neuroimmunomodulation / physiology*
  • Receptors, Adrenergic, beta-2 / deficiency
  • Receptors, Adrenergic, beta-2 / physiology*
  • Specific Pathogen-Free Organisms

Substances

  • ADRB2 protein, mouse
  • Cytokines
  • Receptors, Adrenergic, beta-2
  • Mechanistic Target of Rapamycin Complex 1