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Klebsiella pneumoniae induces inflammatory bowel disease through caspase-11-mediated IL-18 in the gut epithelial cells

  • Author Footnotes
    ∗ Q. Z, X.S, and C.Z contributed equally to this manuscript.
    Qianjin Zhang
    Footnotes
    ∗ Q. Z, X.S, and C.Z contributed equally to this manuscript.
    Affiliations
    Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China

    State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

    Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China
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  • Author Footnotes
    ∗ Q. Z, X.S, and C.Z contributed equally to this manuscript.
    Xiaomin Su
    Footnotes
    ∗ Q. Z, X.S, and C.Z contributed equally to this manuscript.
    Affiliations
    Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China
    Search for articles by this author
  • Author Footnotes
    ∗ Q. Z, X.S, and C.Z contributed equally to this manuscript.
    Chunze Zhang
    Footnotes
    ∗ Q. Z, X.S, and C.Z contributed equally to this manuscript.
    Affiliations
    Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China
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  • Wei Chen
    Affiliations
    Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China

    State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

    Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China
    Search for articles by this author
  • Ya Wang
    Affiliations
    Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China

    State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

    Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China
    Search for articles by this author
  • Xiaorong Yang
    Affiliations
    Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China

    State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

    Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China
    Search for articles by this author
  • Dan Liu
    Affiliations
    Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China

    State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

    Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China
    Search for articles by this author
  • Yuan Zhang
    Affiliations
    Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China

    State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

    Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China
    Search for articles by this author
  • Rongcun Yang
    Affiliations
    Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China

    State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China

    Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China
    Search for articles by this author
  • Author Footnotes
    ∗ Q. Z, X.S, and C.Z contributed equally to this manuscript.
Open AccessPublished:November 24, 2022DOI:https://doi.org/10.1016/j.jcmgh.2022.11.005
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      ABSTRACT

      BACKGROUND AND AIMS

      Klebsiella pneumoniae (KLP), a Gram-negative bacterium belonging to the family of Enterobacteriaceae, is a common cause of antimicrobial-resistant opportunistic infections in hospitalized patients. KLP can colonize in human gastrointestinal tract, especially in patients with inflammatory bowel diseases (IBD). However, effects of KLP on the onset and development of IBD remain unclear.

      METHODS

      We analyzed the relationship between Mayo indexes of ulcerative colitis and KLP using qRT-PCR and endoscopy. Using caspase-1/11-/-, NLRP3-/-, NLRC4-/-, IL-18-/-, and IL-22-/- mice, we demonstrated that KLP could induce colitis through caspase-11 mediated release of mature IL-18. Through in vitro gut organoid culture, we determined the mechanism for KLP to induce colitis.

      RESULTS

      We first found that there was a positive relationship between the Mayo indexes of ulcerative colitis and KLP; Then, we isolated a strain of KLP, named Klebsiella pneumoniae J (KLPJ) from the colon tissues of patients with colitis. This strain of bacteria could induce the production of mature IL-18 in colon epithelial cells and gut organoids, and also induce colitis and promote DSS-mediated colitis. Using caspase-1/11-/-, NLRP3-/-, NLRC4-/-, IL-18-/-, and IL-22-/- mice, we demonstrated that KLPJ-mediated colitis occurred through activation of caspase-11, and was dependent on IL-18 and partly on IL-22. Our data also showed that LPS from KLPJ could bind with caspase-11 to induce mature IL-18 in mouse and human colon organoids.

      CONCLUSIONS

      KLPJ from the colon tissues of patients with ulcerative colitis can colonize the colon, activate caspase-11 inflammasome and contribute to intestinal inflammation.

      Graphical abstract

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