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

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 recepto...

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Autores principales: Kosack, Lindsay, Gawish, Riem, Lercher, Alexander, Vilagos, Bojan, Hladik, Anastasiya, Lakovits, Karin, Bhattacharya, Anannya, Schliehe, Christopher, Mesteri, Ildiko, Knapp, Sylvia, Bergthaler, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595927/
https://www.ncbi.nlm.nih.gov/pubmed/28900132
http://dx.doi.org/10.1038/s41598-017-10637-y
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author Kosack, Lindsay
Gawish, Riem
Lercher, Alexander
Vilagos, Bojan
Hladik, Anastasiya
Lakovits, Karin
Bhattacharya, Anannya
Schliehe, Christopher
Mesteri, Ildiko
Knapp, Sylvia
Bergthaler, Andreas
author_facet Kosack, Lindsay
Gawish, Riem
Lercher, Alexander
Vilagos, Bojan
Hladik, Anastasiya
Lakovits, Karin
Bhattacharya, Anannya
Schliehe, Christopher
Mesteri, Ildiko
Knapp, Sylvia
Bergthaler, Andreas
author_sort Kosack, Lindsay
collection PubMed
description 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.
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spelling pubmed-55959272017-09-15 The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis Kosack, Lindsay Gawish, Riem Lercher, Alexander Vilagos, Bojan Hladik, Anastasiya Lakovits, Karin Bhattacharya, Anannya Schliehe, Christopher Mesteri, Ildiko Knapp, Sylvia Bergthaler, Andreas Sci Rep Article 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. Nature Publishing Group UK 2017-09-12 /pmc/articles/PMC5595927/ /pubmed/28900132 http://dx.doi.org/10.1038/s41598-017-10637-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kosack, Lindsay
Gawish, Riem
Lercher, Alexander
Vilagos, Bojan
Hladik, Anastasiya
Lakovits, Karin
Bhattacharya, Anannya
Schliehe, Christopher
Mesteri, Ildiko
Knapp, Sylvia
Bergthaler, Andreas
The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis
title The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis
title_full The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis
title_fullStr The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis
title_full_unstemmed The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis
title_short The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis
title_sort lipid-sensor trem2 aggravates disease in a model of lcmv-induced hepatitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595927/
https://www.ncbi.nlm.nih.gov/pubmed/28900132
http://dx.doi.org/10.1038/s41598-017-10637-y
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