Metabolic and functional remodeling of colonic macrophages in response to high-fat diet-induced obesity
Angela Castoldi,
David E. Sanin,
Nikki van Teijlingen Bakker,
Cristhiane F. Aguiar,
Lauar de Brito Monteiro,
Nisha Rana,
Katarzyna M. Grzes,
Agnieszka M. Kabat,
Jonathan Curtis,
Alanna M. Cameron,
George Caputa,
Tiago Antônio de Souza,
Fabrício O. Souto,
Joerg M. Buescher,
Joy Edwards-Hicks,
Erika L. Pearce,
Edward J. Pearce,
Niels Olsen Saraiva Camara
Affiliations
Angela Castoldi
Department of Immunology, University of Sao Paulo, Sao Paulo, Brazil; Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany; Institute Keizo Asami, Federal University of Pernambuco, Pernambuco, Brazil
David E. Sanin
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Nikki van Teijlingen Bakker
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany
Cristhiane F. Aguiar
Department of Immunology, University of Sao Paulo, Sao Paulo, Brazil
Lauar de Brito Monteiro
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany
Nisha Rana
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany
Katarzyna M. Grzes
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Agnieszka M. Kabat
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Jonathan Curtis
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Alanna M. Cameron
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany
George Caputa
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany
Tiago Antônio de Souza
Department of Immunology, University of Sao Paulo, Sao Paulo, Brazil
Fabrício O. Souto
Institute Keizo Asami, Federal University of Pernambuco, Pernambuco, Brazil
Joerg M. Buescher
Metabolomics Facility, Max Planck Institute of Epigenetics and Immunobiology, Freiburg im Breisgau, Germany
Joy Edwards-Hicks
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany
Erika L. Pearce
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Edward J. Pearce
Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Niels Olsen Saraiva Camara
Department of Immunology, University of Sao Paulo, Sao Paulo, Brazil; Corresponding author
Summary: Little is known about the effects of high-fat diet (HFD)-induced obesity on resident colonic lamina propria (LP) macrophages (LPMs) function and metabolism. Here, we report that obesity and diabetes resulted in increased macrophage infiltration in the colon. These macrophages exhibited the residency phenotype CX3CR1hiMHCIIhi and were CD4-TIM4-. During HFD, resident colonic LPM exhibited a lipid metabolism gene expression signature that overlapped that used to define lipid-associated macrophages (LAMs). Via single-cell RNA sequencing, we identified a sub-cluster of macrophages, increased in HFD, that were responsible for the LAM signature. Compared to other macrophages in the colon, these cells were characterized by elevated glycolysis, phagocytosis, and efferocytosis signatures. CX3CR1hiMHCIIhi colonic resident LPMs had fewer lipid droplets (LDs) and decreased triacylglycerol (TG) content compared to equivalent cells in lean mice and exhibited increased phagocytic capacity, suggesting that HFD induces adaptive responses in LPMs to limit bacterial translocation.
