title: TLR4-dependent activation of inflammatory cytokine response in macrophages by Francisella elongation factor Tu.
abstract: The bacterial determinants of pulmonary Francisella induced inflammatory responses and their interaction with host components are not clearly defined. In this study, proteomic and immunoblot analyses showed presence of a cytoplasmic protein elongation factor Tu (EF-Tu) in the membrane fractions of virulent Francisella novicida, LVS and SchuS4, but not in an attenuated F. novicida mutant. EF-Tu was immunodominant in mice vaccinated and protected from virulent F. novicida. Moreover, recombinant EF-Tu induced macrophages to produce inflammatory cytokines in a TLR4 dependent manner. This study shows immune stimulatory properties of a cytoplasmic protein EF-Tu expressed on the membrane of virulent Francisella strains.
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249-1644, United States. jyotika.sharma@utsa.edu
authors.forename: Jyotika
authors.initials: J
authors.lastname: Sharma
authors.forename: Bibhuti B
authors.initials: BB
authors.lastname: Mishra
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Judy M
authors.initials: JM
authors.lastname: Teale
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D005603:Francisella / Q000276:immunology* / Q000378:metabolism; D005604:Francisella tularensis / Q000276:immunology / Q000378:metabolism; D007106:Immune Sera / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010444:Peptide Elongation Factor Tu / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007106:Immune Sera; D016056:Immunodominant Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015850:Interleukin-6; D011994:Recombinant Proteins; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D010444:Peptide Elongation Factor Tu