2. Academic Validation
  3. Klebsiella pneumoniae induces inflammatory bowel disease through caspase-11-mediated IL-18 in the gut epithelial cells

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

  • Cell Mol Gastroenterol Hepatol. 2022 Nov 24;S2352-345X(22)00238-7. doi: 10.1016/j.jcmgh.2022.11.005.
Qianjin Zhang 1,  Xiaomin Su 2,  Chunze Zhang 3,  Wei Chen 1,  Ya Wang 1,  Xiaorong Yang 1,  Dan Liu 1,  Yuan Zhang 1,  Rongcun Yang 1
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Immunology, Nankai University School of Medicine; Nankai University, Tianjin 300071, China.
  • 3 Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin 300071, China.
PMID: 36436756 DOI: 10.1016/j.jcmgh.2022.11.005
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.

Keywords

Klebsiella pneumoniae; caspase-11; inflammatory bowel diseases.

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