The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis

Sci Rep. 2017 Sep 12;7(1):11289. doi: 10.1038/s41598-017-10637-y.

Abstract

Lipid metabolism is increasingly being appreciated to affect immunoregulation, inflammation and pathology. In this study we found that mice infected with lymphocytic choriomeningitis virus (LCMV) exhibit global perturbations of circulating serum lipids. Mice lacking the lipid-sensing surface receptor triggering receptor expressed on myeloid cells 2 (Trem2 -/-) were protected from LCMV-induced hepatitis and showed improved virus control despite comparable virus-specific T cell responses. Non-hematopoietic expression of TREM2 was found to be responsible for aggravated hepatitis, indicating a novel role for TREM2 in the non-myeloid compartment. These results suggest a link between virus-perturbed lipids and TREM2 that modulates liver pathogenesis upon viral infection. Targeted interventions of this immunoregulatory axis may ameliorate tissue pathology in hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines
  • Disease Models, Animal
  • Hepatitis / metabolism*
  • Hepatitis / pathology
  • Hepatitis / virology*
  • Lipid Metabolism*
  • Lymphocytic choriomeningitis virus / physiology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Metabolome
  • Metabolomics / methods
  • Mice
  • Mice, Knockout
  • Protein Aggregates
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Viral Load

Substances

  • Cytokines
  • Membrane Glycoproteins
  • Protein Aggregates
  • Receptors, Immunologic
  • Trem2 protein, mouse