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Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice

Author

Listed:
  • Hong Gao

    (University of California, San Diego)

  • Zhenlong Luo

    (University of California, San Diego
    Huazhong University of Science and Technology)

  • Yudong Ji

    (University of California, San Diego
    Huazhong University of Science and Technology)

  • Kechun Tang

    (VA San Diego Healthcare System)

  • Zhongmou Jin

    (University of California, San Diego)

  • Crystal Ly

    (University of California, San Diego)

  • Dorothy D. Sears

    (Arizona State University
    University of California, San Diego
    University of California, San Diego
    University of California, San Diego)

  • Sushil Mahata

    (University of California, San Diego
    VA San Diego Healthcare System)

  • Wei Ying

    (University of California, San Diego)

Abstract

Various microbial products leaked from gut lumen exacerbate tissue inflammation and metabolic disorders in obesity. Vsig4+ macrophages are key players preventing infiltration of bacteria and their products into host tissues. However, roles of islet Vsig4+ macrophages in the communication between microbiota and β cells in pathogenesis of obesity-associated islet abnormalities are unknown. Here, we find that bacterial DNAs are enriched in β cells of individuals with obesity. Intestinal microbial DNA-containing extracellular vesicles (mEVs) readily pass through obese gut barrier and deliver microbial DNAs into β cells, resulting in elevated inflammation and impaired insulin secretion by triggering cGAS/STING activation. Vsig4+ macrophages prevent mEV infiltration into β cells through a C3-dependent opsonization, whereas loss of Vsig4 leads to microbial DNA enrichment in β cells after mEV treatment. Removal of microbial DNAs blunts mEV effects. Loss of Vsig4+ macrophages leads to microbial DNA accumulation in β cells and subsequently obesity-associated islet abnormalities.

Suggested Citation

  • Hong Gao & Zhenlong Luo & Yudong Ji & Kechun Tang & Zhongmou Jin & Crystal Ly & Dorothy D. Sears & Sushil Mahata & Wei Ying, 2022. "Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28239-2
    DOI: 10.1038/s41467-022-28239-2
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