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Enrichment of human IgA-coated bacterial vesicles in ulcerative colitis as a driver of inflammation

Author

Listed:
  • Himadri B. Thapa

    (University of Graz)

  • Christina A. Passegger

    (Medical University of Graz)

  • Dominik Fleischhacker

    (University of Graz)

  • Paul Kohl

    (University of Graz)

  • Yi-Chi Chen

    (University of Zurich)

  • Ratchara Kalawong

    (University of Zurich)

  • Carmen Tam-Amersdorfer

    (Medical University of Graz)

  • Michael R. Gerstorfer

    (Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences)

  • Jana Strahlhofer

    (University of Graz)

  • Kristina Schild-Prüfert

    (University of Graz)

  • Ellen L. Zechner

    (University of Graz
    BioTechMed
    Field of Excellence Biohealth – University of Graz)

  • Andreas Blesl

    (Medical University of Graz)

  • Lukas Binder

    (Medical University of Graz)

  • Georg A. Busslinger

    (Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences)

  • Leo Eberl

    (University of Zurich)

  • Gregor Gorkiewicz

    (BioTechMed
    Medical University of Graz)

  • Herbert Strobl

    (Medical University of Graz
    BioTechMed)

  • Christoph Högenauer

    (BioTechMed
    Medical University of Graz)

  • Stefan Schild

    (University of Graz
    BioTechMed
    Field of Excellence Biohealth – University of Graz
    Institute for Medical Microbiology and Hygiene)

Abstract

The gut microbiome contributes to chronic inflammatory responses in ulcerative colitis (UC), but molecular mechanisms and disease-relevant effectors remain unclear. Here we analyze the pro-inflammatory properties of colonic fluid obtained during colonoscopy from UC and control patients. In patients with UC, we find that the pelletable effector fraction is composed mostly of bacterial extracellular vesicles (BEVs) that exhibit high IgA-levels and incite strong pro-inflammatory responses in IgA receptor-positive (CD89+) immune cells. Biopsy analyses reveal higher infiltration of CD89+ immune cells in the colonic mucosa from patients with UC than control individuals. Further studies show that IgA-coated BEVs, but not host-derived vesicles nor soluble IgA, are potent activators of pro-inflammatory responses in CD89+ cells. IgA-coated BEVs also exacerbate intestinal inflammation in a dextran sodium sulfate colitis model using transgenic mice expressing human CD89. Our data thus implicate a link between IgA-coated BEVs and intestinal inflammation via CD89+ immune cells, and also hint a potential new therapeutic target for UC.

Suggested Citation

  • Himadri B. Thapa & Christina A. Passegger & Dominik Fleischhacker & Paul Kohl & Yi-Chi Chen & Ratchara Kalawong & Carmen Tam-Amersdorfer & Michael R. Gerstorfer & Jana Strahlhofer & Kristina Schild-Pr, 2025. "Enrichment of human IgA-coated bacterial vesicles in ulcerative colitis as a driver of inflammation," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59354-5
    DOI: 10.1038/s41467-025-59354-5
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