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2012全国临床微生物与感染免疫学术研讨会

作者： Wu Minhao~1,Yang Kun~1,Sun Mingxia~(1,2),Peng Anping~1,Huang Xi~(1,2,3) 1.Department of Immunology,Zhongshan School of Medicine,Sun Yat-sen University 2.Department of Anatomy & Cell Biology,Wayne State University School of Medicine 3.State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University

Objectives This study is designed to explore the role of miR-155 inPseudomonas aeruginosa(PA) keratitis,one of the most common sight-threatening ocular diseases. Methods Real-time PCR,Western blot,ocular infection,phagocytosis and killing assay,flow cytometry,immunostaining, bacterial plate count,cell culture and transient transfection,isolation of murine peritoneal macrophages were performed. Results Real-time PCR data suggested that miR-155 expression was enhanced in human and mouse corneas as well as macrophages after PA infection,via a TLR2/4/9and IKK/NF-kappaB/JNK dependent *** determine the role of miR-155 in PA keratitis,C57BL/6(B6) mice were treated with lock nucleic acid anti-miR- 155(an inhibitor of miR-155) by subconjunctival injection together with topical *** of miR- 155 in B6 mice reduced bacterial load and production of Thl/Th17 and pro-inflammatory cytokines,thus promoted host resistance to PA ***,miR-155 knockout B6 mice also displayed a resistant phenotype against PA corneal infection,with lower bacterial burden and ocular inflammation,when compared with wild-type B6 *** further explore the mechanisms of miR-155-mediated immune regulation,we examined the role of miR-155 on inflammatory cytokine production and bacterial clearance in murine bone marrow derived macrophages and macrophage-like RAW264.7 *** vitro studies indicated that in PA-challenged macrophages,miR-155 enhanced the production of Th1/Th17 and pro-inflammatory cytokines,but reduced phagocytosis and killing of PA. We also found that miR-155 inhibited the phagocytosis of PA by down-regulating expression of mannose receptors and complement receptors 3,but not scavenger receptors or IgG Fc fragment receptors,and suppressed the intracellular killing of PA by decreasing nitric oxide but not reactive oxygen species *** addition,our study suggested that miR-155 reduced bacterial clearance and enhanced host inflammation by targeting PI3K p

关键词： Pseudomonas aeruginosa Keratitis microRNA Corneal inflammation bacterial clearance PI3K

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

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Cellular & Molecular Immunology 2023年第10期20卷 1156-1170页

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 Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhenChina Department of Pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Department of Gastroenterology The Seventh Affiliated Hospital of Southern Medical UniversityFoshanChina Department of Critical Care Medicine Nanfang HospitalSouthern Medical UniversityGuangzhouChina Microbiome Medicine Center Zhujiang HospitalSouthern Medical UniversityGuangzhouChina Department of Pathogen Biology Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhouChina Department of Environment and Biosciences School of BusinessInnovation and SustainabilityHalmstad UniversityHalmstadSweden Division of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Medicine University of California San DiegoLa JollaCAUSA

The gut microbiome is recognized as a key modulator of sepsis ***,the contribution of the gut mycobiome to sepsis development is still not fully ***,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 *** 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 ***,PPA directly binds to sirtuin 2(SIRT2)and increases reactive oxygen species(ROS)production for eventual bacterial ***,PPA enhanced the bacterial clearance capacity of macrophages in sepsis patients and was inversely correlated with the severity of sepsis in *** 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

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