Intracellular infection and immune system cues rewire adipocytes to acquire immune function.
George Caputa, Mai Matsushita, David E Sanin, Agnieszka M Kabat, Joy Edwards-Hicks, Katarzyna M Grzes, Roland Pohlmeyer, Michal A Stanczak, Angela Castoldi, Jovana Cupovic, Aaron J Forde, Petya Apostolova, Maximilian Seidl, Nikki van Teijlingen Bakker, Matteo Villa, Francesc Baixauli, Andrea Quintana, Alexandra Hackl, Lea Flachsmann, Fabian Hässler, Jonathan D Curtis, Annette E Patterson, Philipp Henneke, Erika L Pearce, Edward J Pearce
Author Information
George Caputa: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Mai Matsushita: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
David E Sanin: 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.
Agnieszka M Kabat: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Joy Edwards-Hicks: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Katarzyna M Grzes: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Roland Pohlmeyer: Imaging Facility, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Michal A Stanczak: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Angela Castoldi: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Jovana Cupovic: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Aaron J Forde: Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; Center for Chronic Immune Deficiency, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
Petya Apostolova: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Maximilian Seidl: 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.
Nikki van Teijlingen Bakker: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Matteo Villa: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Francesc Baixauli: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Andrea Quintana: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Alexandra Hackl: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Lea Flachsmann: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Fabian Hässler: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Jonathan D Curtis: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Annette E Patterson: Department of Immunometabolism, Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Philipp Henneke: Center for Chronic Immune Deficiency, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
Erika L Pearce: 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.
Edward J Pearce: 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.
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.
