title: Igh-6(-/-) (B-cell-deficient) mice fail to mount solid acquired resistance to oral challenge with virulent Salmonella enterica serovar typhimurium and show impaired Th1 T-cell responses to Salmonella antigens.
abstract: In the present study we evaluated the role of B cells in acquired immunity to Salmonella infection by using gene-targeted B-cell-deficient innately susceptible mice on a C57BL/6 background (Igh-6(-/-)). Igh-6(-/-) mice immunized with a live, attenuated aroA Salmonella enterica serovar Typhimurium vaccine strain showed impaired long-term acquired resistance against the virulent serovar Typhimurium strain C5. Igh-6(-/-) mice were able to control a primary infection and to clear the inoculum from the reticuloendothelial system. However, Igh-6(-/-) mice, unlike Igh-6(+/+) C57BL/6 controls, did not survive an oral challenge with strain C5 at 4 months after vaccination. Transfer of immune serum did not restore resistance in Igh-6(-/-) mice. Total splenocytes and purified CD4(+) T cells obtained from Igh-6(-/-) mice 4 months after vaccination showed reduced ability to release Th1-type cytokines (interleukin 2 and gamma interferon) upon in vitro restimulation with serovar Typhimurium soluble cell extracts compared to cells obtained from Igh-6(+/+) C57BL/6 control mice. Therefore, the impaired resistance to oral challenge with virulent serovar Typhimurium observed in B-cell-deficient mice, which cannot be restored by passive transfer of Salmonella-immune serum, may be in part due to a reduced serovar Typhimurium-specific T-cell response following primary immunization.
authors.affiliation: Centre for Veterinary Science, University of Cambridge, Cambridge CB3 OES, United Kingdom. pm274@cam.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Mastroeni
authors.forename: C
authors.initials: C
authors.lastname: Simmons
authors.forename: R
authors.initials: R
authors.lastname: Fowler
authors.forename: C E
authors.initials: CE
authors.lastname: Hormaeche
authors.forename: G
authors.initials: G
authors.lastname: Dougan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage; D005260:Female; D005803:Genes, Immunoglobulin; D007114:Immunization; D007116:Immunization, Passive; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007143:Immunoglobulin Heavy Chains; D007376:Interleukin-2; D014613:Vaccines, Attenuated; D007371:Interferon-gamma