title: Wild-type and mutant AvrA- Salmonella induce broadly similar immune pathways in the chicken ceca with key differences in signaling intermediates and inflammation.
abstract: Salmonella enterica serovar Typhimurium (ST) is a serious infectious disease throughout the world, and a major reservoir for Salmonella is chicken. Chicken infected with Salmonella do not develop clinical disease, this may be the result of important host interactions with key virulence proteins. To study this, we inoculated chicken with mutant Salmonella Typhimurium that lacked the virulence protein AvrA (AvrA(-)). AvrA is referred to as an avirulence factor, as it moderates the host immune response. The lack of the AvrA virulence gene in ST resulted in reduced weight gain, enhanced persistence and greater extraintestinal organ invasion in chickens, as compared to wild-type (WT) ST. Kinome analysis was performed on inoculated cecal tissue. The majority of the signal transduction pathways induced by AvrA(-) and WT ST were similar; however, we observed alterations in innate immune system signaling. In addition, a leukocyte migration pathway was altered by AvrA(-) ST that may allow greater gut barrier permeability and invasion by the mutant. Cytokine expression did not appear significantly altered at 7 d post-inoculation; at 14 d post-inoculation, there was an observed increase in the expression of anti-inflammatory IL-10 in the WT inoculated ceca. This study is the first to describe mutant AvrA(-) ST infection of chicken and provides further insight into the Salmonella responses observed in chicken relative to other species such as humans and cattle.
authors.affiliation: Department of Animal and Food Sciences, University of Delaware, 531 S. College Ave, Newark, DE rja@udel.edu.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Arsenault
authors.affiliation: Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Genovese
authors.affiliation: Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX.
authors.forename: Haiqi
authors.initials: H
authors.lastname: He
authors.affiliation: Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Huixia
authors.initials: H
authors.lastname: Wu
authors.affiliation: Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Neish
authors.affiliation: Southern Plains Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, 2881 F&B Road, College Station, TX.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kogut
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002432:Cecum / Q000382:microbiology; D002645:Chickens; D007113:Immunity, Innate; D011201:Poultry Diseases / Q000276:immunology* / Q000382:microbiology; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000276:immunology*; D015398:Signal Transduction; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C487891:AvrA protein, Salmonella typhimurium; D001426:Bacterial Proteins; D037521:Virulence Factors
keywords: AvrA; Salmonella Typhimurium; immunology; kinome; peptide array