Age-associated accumulation of B cells promotes macrophage inflammation and inhibits lipolysis in adipose tissue during sepsis
Anna Carey,
Katie Nguyen,
Pranathi Kandikonda,
Victor Kruglov,
Claire Bradley,
Korbyn J.V. Dahlquist,
Stephanie Cholensky,
Whitney Swanson,
Vladimir P. Badovinac,
Thomas S. Griffith,
Christina D. Camell
Affiliations
Anna Carey
Molecular Pharmacology and Therapeutics Graduate Program, Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Katie Nguyen
Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Pranathi Kandikonda
Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Victor Kruglov
Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Claire Bradley
Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Korbyn J.V. Dahlquist
Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Stephanie Cholensky
Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
Whitney Swanson
Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA
Vladimir P. Badovinac
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Thomas S. Griffith
Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA; Minneapolis VA Health Care System, Minneapolis, MN 55417, USA
Christina D. Camell
Molecular Pharmacology and Therapeutics Graduate Program, Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding author
Summary: Non-canonical lipolysis induced by inflammatory cytokines or Toll-like receptor ligands is required for the regulation of inflammation during endotoxemia and sepsis. Canonical lipolysis induced by catecholamines declines during aging due to factors including an expansion of lymphocytes, pro-inflammatory macrophage polarization, and an increase in chronic low-grade inflammation; however, the extent to which the non-canonical pathway of lipolysis is active and impacted by immune cells during aging remains unclear. Therefore, we aimed to define the extent to which immune cells from old mice influence non-canonical lipolysis during sepsis. We identified age-associated impairments of non-canonical lipolysis and an accumulation of dysfunctional B1 B cells in the visceral white adipose tissue (vWAT) of old mice. Lifelong deficiency of B cells results in restored non-canonical lipolysis and reductions in pro-inflammatory macrophage populations. Our study suggests that targeting the B cell-macrophage signaling axis may resolve metabolic dysfunction in aged vWAT and attenuate septic severity in older individuals.
