White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection

Seong-Ji Han; Arielle Glatman Zaretsky; Vinicius Andrade-Oliveira; Nicholas Collins; Amiran Dzutsev; Jahangheer Shaik; Denise Morais da Fonseca; Oliver J Harrison; Samira Tamoutounour; Allyson L Byrd; Margery Smelkinson; Nicolas Bouladoux; James B Bliska; Jason M Brenchley; Igor E Brodsky; Yasmine Belkaid

doi:10.1016/j.immuni.2017.11.009

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection

Immunity. 2017 Dec 19;47(6):1154-1168.e6. doi: 10.1016/j.immuni.2017.11.009. Epub 2017 Dec 5.

Authors

Seong-Ji Han¹, Arielle Glatman Zaretsky¹, Vinicius Andrade-Oliveira¹, Nicholas Collins¹, Amiran Dzutsev², Jahangheer Shaik¹, Denise Morais da Fonseca¹, Oliver J Harrison¹, Samira Tamoutounour¹, Allyson L Byrd³, Margery Smelkinson⁴, Nicolas Bouladoux⁵, James B Bliska⁶, Jason M Brenchley⁷, Igor E Brodsky⁸, Yasmine Belkaid⁹

Affiliations

¹ Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
² Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
³ Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA; Department of Bioinformatics, Boston University, Boston, MA 02215, USA.
⁴ Biological Imaging, Research Technology Branch, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
⁵ Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; NIAID Microbiome Program, NIH, Bethesda, MD 20892, USA.
⁶ Department of Molecular Genetics and Microbiology, 238 Centers for Molecular Medicine, Stony Brook University, Stonybrook, NY 11794, USA.
⁷ Barrier Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
⁸ Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹ Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; NIAID Microbiome Program, NIH, Bethesda, MD 20892, USA. Electronic address: ybelkaid@niaid.nih.gov.

Abstract

White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge. Induction of recall responses within white adipose tissue was associated with the collapse of lipid metabolism in favor of antimicrobial responses. Our results suggest that white adipose tissue represents a memory T cell reservoir that provides potent and rapid effector memory responses, positioning this compartment as a potential major contributor to immunological memory.

Keywords: T cells; adipocytes; adipose tissue; central memory T cells; effector memory T cells; infection; lipids; memory; metabolism; resident memory T cells.

Published by Elsevier Inc.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

MeSH terms

Adipose Tissue, White / immunology
Adipose Tissue, White / transplantation*
Animals
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / microbiology
CD4-Positive T-Lymphocytes / parasitology
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / microbiology
CD8-Positive T-Lymphocytes / parasitology
Gene Expression
Genes, Reporter
Immunologic Memory*
Interferon-gamma / genetics
Interferon-gamma / immunology
Interleukin-17 / genetics
Interleukin-17 / immunology
Interleukin-5 / genetics
Interleukin-5 / immunology
Lipid Metabolism
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Survival Analysis
Tissue Transplantation
Toxoplasma / immunology
Toxoplasmosis / genetics
Toxoplasmosis / immunology*
Toxoplasmosis / mortality
Toxoplasmosis / parasitology
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / immunology
Yersinia pseudotuberculosis / immunology
Yersinia pseudotuberculosis Infections / genetics
Yersinia pseudotuberculosis Infections / immunology*
Yersinia pseudotuberculosis Infections / microbiology
Yersinia pseudotuberculosis Infections / mortality

Substances

Bacterial Proteins
Interleukin-17
Interleukin-5
Luminescent Proteins
Tumor Necrosis Factor-alpha
yellow fluorescent protein, Bacteria
Interferon-gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding