title: Expression, production and release of the Eis protein by Mycobacterium tuberculosis during infection of macrophages and its effect on cytokine secretion.
abstract: The eis gene of Mycobacterium tuberculosis has been shown to play a role in the survival of the avirulent Mycobacterium smegmatis within the macrophage. In vitro and in vivo analysis of Deltaeis deletion mutants and complemented strains showed no effect on survival of M. tuberculosis in U-937 macrophages or in a mouse aerosol infection model, respectively. Further studies were done in an attempt to determine the role of eis in M. tuberculosis intracellular survival and to define a phenotypic difference between wild-type and the Deltaeis deletion mutant. Bioinformatic analysis indicated that Eis is an acetyltransferase of the GCN5-related family of N-acetyltransferases. Immunofluorescence microscopy and Western blot analysis studies demonstrated that Eis is released into the cytoplasm of M. tuberculosis-infected U-937 macrophages. Eis was also found in the extravesicular fraction and culture supernatant of M. tuberculosis-infected macrophages. The effect of Eis on human macrophage cytokine secretion was also examined. Eis modulated the secretion of IL-10 and TNF-alpha by primary human monocytes in response both to infection with M. tuberculosis and to stimulation with recombinant Eis protein. These results suggest that Eis is a mycobacterial effector that is released into the host cell to modulate inflammatory responses, possibly via transcriptional or post-translational means.
authors.affiliation: Department of Microbiology and Immunology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Linoj P
authors.initials: LP
authors.lastname: Samuel
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Song
authors.affiliation: Department of Microbiology and Immunology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Microbiology and Immunology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Esteban A
authors.initials: EA
authors.lastname: Roberts
authors.affiliation: School of Molecular Bioscience, Washington State University, Pullman, WA 99164, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Dahl
authors.affiliation: Tuberculosis Research Section, National Institute of Allergy and Infectious Disease, Rockville, MD 20852, USA.
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.affiliation: Department of Microbiology and Immunology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Friedman
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D016207:Cytokines / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D020298:U937 Cells; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D000123:Acetyltransferases; C430563:Eis protein, Mycobacterium tuberculosis