Intracellular infection and immune system cues rewire adipocytes to acquire immune function

George Caputa¹, Mai Matsushita¹, David E Sanin², Agnieszka M Kabat¹, Joy Edwards-Hicks¹, Katarzyna M Grzes¹, Roland Pohlmeyer³, Michal A Stanczak¹, Angela Castoldi¹, Jovana Cupovic¹, Aaron J Forde⁴, Petya Apostolova¹, Maximilian Seidl⁵, Nikki van Teijlingen Bakker⁶, Matteo Villa¹, Francesc Baixauli¹, Andrea Quintana¹, Alexandra Hackl¹, Lea Flachsmann¹, Fabian Hässler¹, Jonathan D Curtis¹, Annette E Patterson¹, Philipp Henneke⁷, Erika L Pearce⁸, Edward J Pearce⁹

Affiliations

¹ Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
² Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Bloomberg Kimmel Institute, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
³ Imaging Facility, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
⁴ Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; Center for Chronic Immune Deficiency, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
⁵ Center for Chronic Immune Deficiency, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Institute of Surgical Pathology, Faculty of Medicine, Medical Center, University of Freiburg, 79104 Freiburg, Germany; Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany.
⁶ Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
⁷ Center for Chronic Immune Deficiency, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
⁸ Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Bloomberg Kimmel Institute, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA. Electronic address: epearce6@jhmi.edu.
⁹ Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; Bloomberg Kimmel Institute, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA. Electronic address: epearce7@jhmi.edu.

PMID: 35508110
DOI: 10.1016/j.cmet.2022.04.008

Free article

Intracellular infection and immune system cues rewire adipocytes to acquire immune function

George Caputa et al. Cell Metab. 2022.

Free article

. 2022 May 3;34(5):747-760.e6.

doi: 10.1016/j.cmet.2022.04.008.

Authors

Affiliations

¹ Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
² Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Bloomberg Kimmel Institute, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
³ Imaging Facility, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
⁴ Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; Center for Chronic Immune Deficiency, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
⁵ Center for Chronic Immune Deficiency, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Institute of Surgical Pathology, Faculty of Medicine, Medical Center, University of Freiburg, 79104 Freiburg, Germany; Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany.
⁶ Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
⁷ Center for Chronic Immune Deficiency, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
⁸ Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Bloomberg Kimmel Institute, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA. Electronic address: epearce6@jhmi.edu.
⁹ Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; Bloomberg Kimmel Institute, and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA. Electronic address: epearce7@jhmi.edu.

PMID: 35508110
DOI: 10.1016/j.cmet.2022.04.008

Abstract

Adipose tissue (AT) plays a central role in systemic metabolic homeostasis, but its function during bacterial infection remains unclear. Following subcutaneous bacterial infection, adipocytes surrounding draining lymph nodes initiated a transcriptional response indicative of stimulation with IFN-γ and a shift away from lipid metabolism toward an immunologic function. Natural killer (NK) and invariant NK T (iNKT) cells were identified as sources of infection-induced IFN-γ in perinodal AT (PAT). IFN-γ induced Nos2 expression in adipocytes through a process dependent on nuclear-binding oligomerization domain 1 (NOD1) sensing of live intracellular bacteria. iNOS expression was coupled to metabolic rewiring, inducing increased diversion of extracellular L-arginine through the arginosuccinate shunt and urea cycle to produce nitric oxide (NO), directly mediating bacterial clearance. In vivo, control of infection in adipocytes was dependent on adipocyte-intrinsic sensing of IFN-γ and expression of iNOS. Thus, adipocytes are licensed by innate lymphocytes to acquire anti-bacterial functions during infection.

Keywords: IFN-γ; NK cells; NOD1; NOS2; adipocyte; iNK T cells; infection; lymph node; metabolism; perinodal adipose tissue.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests E.J.P. and E.L.P. are founders of Rheos Medicines. E.L.P. is an SAB member of ImmunoMet.

Comment in

A FAsT contribution: Adipocytes rewire their metabolism to acquire immune functions.
Kobayashi T, Brenner D. Kobayashi T, et al. Cell Metab. 2022 May 3;34(5):656-657. doi: 10.1016/j.cmet.2022.04.007. Cell Metab. 2022. PMID: 35508107

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science
Molecular Biology Databases
- Mouse Genome Informatics (MGI)

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Intracellular infection and immune system cues rewire adipocytes to acquire immune function

Affiliations

Intracellular infection and immune system cues rewire adipocytes to acquire immune function

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Molecular Biology Databases