Klebsiella pneumoniae Induces Inflammatory Bowel Disease Through Caspase-11–Mediated IL18 in the Gut Epithelial CellsSummary

Qianjin Zhang; Xiaomin Su; Chunze Zhang; Wei Chen; Ya Wang; Xiaorong Yang; Dan Liu; Yuan Zhang; Rongcun Yang

Cellular and Molecular Gastroenterology and Hepatology (Jan 2023)

Klebsiella pneumoniae Induces Inflammatory Bowel Disease Through Caspase-11–Mediated IL18 in the Gut Epithelial CellsSummary

Qianjin Zhang,
Xiaomin Su,
Chunze Zhang,
Wei Chen,
Ya Wang,
Xiaorong Yang,
Dan Liu,
Yuan Zhang,
Rongcun Yang

Affiliations

Qianjin Zhang: Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
Xiaomin Su: Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
Chunze Zhang: Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China
Wei Chen: Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
Ya Wang: Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
Xiaorong Yang: Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
Dan Liu: Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
Yuan Zhang: Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
Rongcun Yang: Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China; Correspondence Address correspondence to: Rongcun Yang, MD, PhD, Department of Immunology, Nankai University School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.

Journal volume & issue: Vol. 15, no. 3
pp. 613 – 632

Abstract

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Background & 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 the human gastrointestinal tract, especially in patients with inflammatory bowel diseases. However, effects of KLP on the onset and development of inflammatory bowel disease remain unclear. Methods: We analyzed the relationship between Mayo indexes of ulcerative colitis and KLP using quantitative reverse-transcription polymerase chain reaction and endoscopy. Using caspase-1/11-/-, NLRP3-/-, NLRC4-/-, interleukin (IL)18-/-, and IL22-/- mice, we showed that KLP could induce colitis through caspase-11–mediated release of mature IL18. 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 IL18 in colon epithelial cells and gut organoids, and also induce colitis and promote dextran sodium sulfate–mediated colitis. Using caspase-1/11-/-, NLRP3-/-, NLRC4-/-, IL18-/-, and IL22-/- mice, we showed that KLPJ-mediated colitis occurred through activation of caspase-11, and was dependent on IL18 and partly on IL22. Our data also showed that lipopolysaccharide from KLPJ could bind with caspase-11 to induce mature IL18 in mouse and human colon organoids. Conclusions: KLPJ from the colon tissues of patients with ulcerative colitis can colonize the colon, activate caspase-11 inflammasomes, and contribute to intestinal inflammation.

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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