title: Distinct innate responses are induced by attenuated Salmonella enterica serovar Typhimurium mutants.
abstract: Upon bacterial infection the host cells generate a wide variety of cytokines. Genetic attenuation of bacterial physiological pathogens can be accomplished not only by disruption of normal bacterial processes, but also by the loss of the ability to redirect the host immune system. We examined nine attenuated Salmonella Typhimurium mutants for their ability to replicate as well as the cytokines produced after infection of Bone Marrow Derived Macrophages (BMDM). Infection of BMDM with attenuated Salmonella mutants led to host cytokine patterns distinct from those that followed WT infection. Surprisingly, each bacterial mutant had a unique cytokine signature. Because some of the mutants induced an IL-10 response not seen in WT, we examined the role of IL-10 on Salmonella replication. Surprisingly, addition of IL-10 before or concurrent with infection restricted growth of WT Salmonella in BMDM. Bacterial attenuation is not a single process and results in attenuated host responses, which result in unique patterns for each attenuated mutants.
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85719, United States. Electronic address: danielpowell@email.arizona.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Powell
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85719, United States.
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Roberts
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85719, United States.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Ledvina
authors.affiliation: Duke Human Vaccine Institute, Durham, NC 27710, United States.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.affiliation: Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85281, United States.
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85719, United States.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Frelinger
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009154:Mutation; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000276:immunology*
chemical_list: D016207:Cytokines; D016753:Interleukin-10
keywords: Attenuation; Innate immunity; Salmonella