Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling

  • Pailin Chiaranunt
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Kyle Burrows
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Louis Ngai
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Siu Ling Tai
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Eric Y. Cao
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Helen Liang
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Homaira Hamidzada
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Anthony Wong
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Julia Gschwend
    Institute of Physiology, University of Zürich, Zürich, Switzerland.
  • Pascal Flüchter
    Institute of Physiology, University of Zürich, Zürich, Switzerland.
  • Meggie Kuypers
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Tijana Despot
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Abdul Momen
    Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
  • Sung Min Lim
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Thierry Mallevaey
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Christoph Schneider
    Institute of Physiology, University of Zürich, Zürich, Switzerland.
  • Tyrrell Conway
    Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK, USA.
  • Hiromi Imamura
    Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
  • Slava Epelman
    Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Arthur Mortha
    Department of Immunology, University of Toronto, Toronto, ON, Canada.

Description

<jats:p>Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically guide intestinal MΦ development, although the exact nature, regulation, and location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated lymphoid tissues (SILTs) in a cell-extrinsic, NLRP3/P2X7R-dependent fashion in the steady state. Tissue-infiltrating monocytes accumulating around SILTs followed a spatially constrained, distinct developmental trajectory into SILT-associated MΦs (SAMs). CSF2 regulated the mitochondrial membrane potential and reactive oxygen species production of SAMs and contributed to the antimicrobial defense against enteric bacterial infections. Collectively, these findings identify SILTs and CSF2-producing ILC3s as a microanatomic niche for intestinal MΦ development and functional programming fueled by the integration of commensal microbial energy metabolism.</jats:p>

Journal

  • Science Immunology

    Science Immunology 8 (86), 2023-08-04

    American Association for the Advancement of Science (AAAS)

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