title: Heat-killed and γ-irradiated Brucella strain RB51 stimulates enhanced dendritic cell activation, but not function compared with the virulent smooth strain 2308.
abstract: Brucella spp. are Gram-negative, facultative intracellular bacterial pathogens that cause abortion in livestock and undulant fever in humans worldwide. Brucella abortus strain 2308 is a pathogenic strain that affects cattle and humans. Currently, there are no efficacious human vaccines available. However, B. abortus strain RB51, which is approved by the USDA, is a live-attenuated rough vaccine against bovine brucellosis. Live strain RB51 induces protection via CD4(+) and CD8(+) T-cell-mediated immunity. To generate an optimal T-cell response, strong innate immune responses by dendritic cells (DCs) are crucial. Because of safety concerns, the use of live vaccine strain RB51 in humans is limited. Therefore, in this study, we analyzed the differential ability of the same doses of live, heat-killed (HK) and γ-irradiated (IR) strain RB51 in inducing DC activation and function. Smooth strain 2308, live strain RB51 and lipopolysaccharide were used as controls. Studies using mouse bone marrow-derived DCs revealed that, irrespective of viability, strain RB51 induced greater DC activation than smooth strain 2308. Live strain RB51 induced significantly (P≤0.05) higher DC maturation than HK and IR strains, and only live strain RB51-infected DCs (at multiplicity of infection 1:100) induced significant (P≤0.05) tumor necrosis factor-α and interleukin-12 secretion.
authors.affiliation: Department of Large Animal Clinical Sciences, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Surendran
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hiltbold
authors.forename: Bettina
authors.initials: B
authors.lastname: Heid
authors.forename: Nammalwar
authors.initials: N
authors.lastname: Sriranganathan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Boyle
authors.forename: Kurt L
authors.initials: KL
authors.lastname: Zimmerman
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Witonsky
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000032:analysis; D015373:Bacterial Typing Techniques; D002004:Brucella Vaccine / Q000276:immunology*; D002003:Brucella abortus / Q000276:immunology* / Q000472:pathogenicity / Q000528:radiation effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005720:Gamma Rays; D006358:Hot Temperature; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D051940:B7-2 Antigen; D002004:Brucella Vaccine; D019013:CD40 Antigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D018664:Interleukin-12