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Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin

  1. Author:
    Voisin, Benjamin
    Nadella, Vinod
    Doebel, Thomas
    Goel, Shubham
    Sakamoto, Keiko
    Ayush, Otgonzaya
    Jo, Jay-Hyun
    Kelly,Michael
    Kobayashi, Tetsuro
    Jiang, Jean X
    Hu, Ying
    Yan, Chunhua
    Nagao, Keisuke

  2. Author Address

    Cutaneous Leukocyte Biology Section, Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA., Cutaneous Microbiome and Inflammation Section, Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA., Cancer Research Technology Program, Single-Cell Analysis Facility, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA., Cancer Informatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, Rockville, MD, USA., Cutaneous Leukocyte Biology Section, Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: keisuke.nagao@nih.gov.,
    1. Year: 2023
    2. Date: Jul 11
    3. Epub Date: 2023 07 03
  2. Journal: Immunity
    1. 56
    2. 7
    3. Pages: 1561-1577.e9
  4. Type of Article: Article
  1. Abstract:

    Hypodermis is the predominant site of Staphylococcus aureus infections that cause cellulitis. Given the importance of macrophages in tissue remodeling, we examined the hypodermal macrophages (HDMs) and their impact on host susceptibility to infection. Bulk and single-cell transcriptomics uncovered HDM subsets with CCR2-dichotomy. HDM homeostasis required the fibroblast-derived growth factor CSF1, ablation of which abrogated HDMs from the hypodermal adventitia. Loss of CCR2- HDMs resulted in accumulation of the extracellular matrix component, hyaluronic acid (HA). HDM-mediated HA clearance required sensing by the HA receptor, LYVE-1. Cell-autonomous IGF1 was required for accessibility of AP-1 transcription factor motifs that controlled LYVE-1 expression. Remarkably, loss of HDMs or IGF1 limited Staphylococcus aureus expansion via HA and conferred protection against cellulitis. Our findings reveal a function for macrophages in the regulation of HA with an impact on infection outcomes, which may be harnessed to limit the establishment of infection in the hypodermal niche. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.immuni.2023.06.006
  3. PMID: 37402364
  4. View record in Web of Science®
  5. WOS: 001049193200001
  6. PII : S1074-7613(23)00263-7

Library Notes

  1. Fiscal Year: FY2022-2023
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