A metabolite from commensal Candida albicans enhances the bactericidal activity of macrophages and protects against sepsis  

作　　者：Peng Gu Ruofan Liu Qin Yang Li Xie Rongjuan Wei Jiaxin Li Fengyi Mei Tao Chen Zhenhua Zeng Yan He Hongwei Zhou Hongjuan Peng Kutty Selva Nandakumar Huikuan Chu Yong Jiang Wei Gong Ye Chen Bernd Schnabl Peng Chen 

机构地区：[1]Department of Gastroenterology,Shenzhen Hospital,Southern Medical University,Shenzhen,China [2]Department of Pathophysiology,Guangdong Provincial Key Laboratory of Proteomics,School of Basic Medical Sciences,Southern Medical University,Guangzhou,China [3]Department of Gastroenterology,The Seventh Affiliated Hospital of Southern Medical University,Foshan,China [4]Department of Critical Care Medicine,Nanfang Hospital,Southern Medical University,Guangzhou,China [5]Microbiome Medicine Center,Zhujiang Hospital,Southern Medical University,Guangzhou,China [6]Department of Pathogen Biology,Guangdong Provincial Key Laboratory of Tropical Disease Research,School of Public Health,Southern Medical University,Guangzhou,China [7]Department of Environment and Biosciences,School of Business,Innovation and Sustainability,Halmstad University,Halmstad,Sweden [8]Division of Gastroenterology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [9]Department of Medicine,University of California San Diego,La Jolla,CA,USA

出　　处：《Cellular & Molecular Immunology》2023年第10期1156-1170,共15页中国免疫学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(32271230 and 32071124)to PC;the NIH Grant(P30DK120515)to BS;the National Natural Science Foundation of China(82270581)to YC;the National Key R&D Project of China(2018YFC0115301);the National Natural Science Foundation of China(81974070);the Shenzhen Science and Technology Program(JCYJ20210324131010027);the Research Foundation of Shenzhen Hospital of Southern Medical University(PT2018GZR10)to WG.

摘　　要：The gut microbiome is recognized as a key modulator of sepsis development.However,the contribution of the gut mycobiome to sepsis development is still not fully understood.Here,we demonstrated that the level of Candida albicans was markedly decreased in patients with bacterial sepsis,and the supernatant of Candida albicans culture significantly decreased the bacterial load and improved sepsis symptoms in both cecum ligation and puncture(CLP)-challenged mice and Escherichia coli-challenged pigs.Integrative metabolomics and the genetic engineering of fungi revealed that Candida albicans-derived phenylpyruvate(PPA)enhanced the bactericidal activity of macrophages and reduced organ damage during sepsis.Mechanistically,PPA directly binds to sirtuin 2(SIRT2)and increases reactive oxygen species(ROS)production for eventual bacterial clearance.Importantly,PPA enhanced the bacterial clearance capacity of macrophages in sepsis patients and was inversely correlated with the severity of sepsis in patients.Our findings highlight the crucial contribution of commensal fungi to bacterial disease modulation and expand our understanding of the host-mycobiome interaction during sepsis development.

关 键 词：Candida albicans Phenylpyruvate SEPSIS MACROPHAGE Bacterial clearance 

分 类 号：R591.3[医药卫生—内科学] R552[医药卫生—临床医学]