title: Role of eosinophils and apoptosis in PDIMs/PGLs deficient mycobacterium elimination in adult zebrafish.
abstract: The cell wall lipids phthiocerol dimycocerosates (PDIMs) and its structurally-related compound, phenolic glycolipids (PGLs) are major virulence factors of mycobacterium, as shown by the reduced growth of PDIMs/PGLs deficient mutants in various animal models. PDIMs/PGLs play active roles in modulating host immune responses. However, the cellular and molecular mechanisms of how PDIMs/PGLs deficient mutant was eliminated in vivo are still elusive. Our aim was to investigate what host immune responses have effect on mycobacterium elimination in vivo. Using microarray, we find PDIMs/PGLs modulate divergent host responses, including chemotaxis and focal adhesion's downstream pathway and apoptosis. We examine these two host responses by Diff-Quik stain, coupled with transmission electron microscopy and TUNEL stain respectively. The ultrastructure observation showed that eosinophils appeared in WT-infected zebrafish at day 1, however eosinophils arrived was delayed to day 7 in PDIMs/PGLs-deficient mutant-infected animals. More intriguingly, apoptosis was markedly increased in PDIMs/PGLs-mutant infected zebrafish at day 1 after infection, compared to WT-infected fishes at this time. However, apoptosis trend was fully reversed by day 7, with increased apoptosis were detected in WT-infected zebrafish compared with the PDIMs/PGLs-deficient mutant, especially more apoptosis within the granuloma. This study shows that the anti-apoptotic effects of PDIMs/PGLs and the recruitment of eosinophils in tissue during the early infection in zebrafish might promote bacterium growth in vivo.
authors: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China.
authors: Xinhua
authors: X
authors: Huang
authors: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China.
authors: Hui
authors: H
authors: Wang
authors: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China.
authors: Lu
authors: L
authors: Meng
authors: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China.
authors: Qinglan
authors: Q
authors: Wang
authors: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China.
authors: Jia
authors: J
authors: Yu
authors: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China.
authors: Qian
authors: Q
authors: Gao
authors: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China; Medical College of China Three Gorges University, Hubei, 443002 PR China. Electronic address: dcwang99@163.com.
authors: Decheng
authors: D
authors: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000276:immunology*; D002473:Cell Wall / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D005393:Fish Diseases / Q000276:immunology* / Q000382:microbiology; D006017:Glycolipids / Q000235:genetics; D008055:Lipids / Q000235:genetics / Q000494:pharmacology*; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology* / Q000382:microbiology; D019910:Mycobacterium marinum / Q000276:immunology / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: D016207:Cytokines; D006017:Glycolipids; D008055:Lipids; D037521:Virulence Factors; C008901:phthiocerol dimycocerosate
keywords: Apoptosis; Eosinophils; Mycobacterium marinum (M. marinum); PDIMs; PGLs