Liver abscess induced by intestinal hypervirulent Klebsiella pneumoniae through down-regulation of tryptophan-IPA-IL22 axis
Xiu You,
Liping Wang,
Hong Wang,
Yizheng Xu,
Yongzheng Chen,
Huizhen Xu,
Xuelian Ji,
Xiangsong Ma,
Xiuyu Xu
Affiliations
Xiu You
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
Liping Wang
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
Hong Wang
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
Yizheng Xu
Key Laboratory of Laboratory Medical Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; Department of Clinical Laboratory, Sichuan Orthopedic Hospital, Chengdu, Sichuan 610000, China
Yongzheng Chen
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
Huizhen Xu
Key Laboratory of Laboratory Medical Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China
Xuelian Ji
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Xiangsong Ma
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Xiuyu Xu
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Corresponding author
Summary: Hypervirulent Klebsiella pneumoniae (hvKp) is a significant causative agent of invasive hepatic abscess syndrome in Asia, presenting substantial clinical challenges due to its intricate pathogenesis. This study revealed the crucial role of the gut microbiota in fortifying the host’s defense against hvKp infection by enhancing interleukin-22 (IL-22), probably through regulating downstream antimicrobial peptides such as Reg3β. In antibiotic-treated mice, we observed that gut microbiota disruption impaired the transformation of tryptophan to indole, a key ligand for the aryl hydrocarbon receptor (AhR), consequently affecting the regulatory functions of IL-22. Our experimental findings revealed that administering rIL-22 or indole propionic acid notably diminished the translocation of hvKp from the intestine to the liver. This research not only underscores the pivotal role of the gut microbiome in modulating tryptophan metabolism and the IL-22 pathway but also highlights its critical function in preventing hvKp migration from the colon to the liver.
