title: Innate immunity mediated by MyD88 signal is not essential for induction of lipopolysaccharide-specific B cell responses but is indispensable for protection against Salmonella enterica serovar Typhimurium infection.
abstract: Salmonella organisms are Gram negative and facultative anaerobic bacteria that cause typhoid fever in humans. In this study, we evaluated LPS-specific adaptive immunity in innate immune-deficient mice after oral administration of attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) strains. Of interest, identical levels of LPS-specific IgG and IgA Abs were elicited in the systemic (i.e., serum and spleen) and mucosal (i.e., fecal extract and small intestine) compartments of wild-type, TLR4(-/-), and MyD88(-/-) mice following oral vaccination with recombinant attenuated S. Typhimurium (RASV). Depletion of CD4(+) T cells during RASV vaccination completely abrogated the generation of LPS-specific Abs in MyD88(-/-) mice. In addition, mRNA expression levels of a B cell-activating factor of the TNF family were significantly increased in the spleens of MyD88(-/-) mice after oral administration, implying that T cell-independent B cell switching might be also enhanced in the MyD88 signal-deficient condition. Of most interest, orally vaccinated MyD88(-/-) mice that possessed high levels of LPS-specific IgG and IgA, which had a neutralizing effect against Salmonella, died earlier than nonvaccinated wild-type mice following lethal oral challenge with virulent Salmonella species. These results suggest that innate immunity mediated by MyD88 signal is dispensable for induction of LPS-specific Ab responses following oral administration of attenuated Salmonella strains but indispensable for efficient protection.
authors.affiliation: Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Korea.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Yang
authors.forename: Doo-Hee
authors.initials: DH
authors.lastname: Shim
authors.forename: Hyungjun
authors.initials: H
authors.lastname: Yang
authors.forename: Sung-Moo
authors.initials: SM
authors.lastname: Park
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012480:Salmonella Infections / Q000276:immunology*; D022562:Salmonella Vaccines / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D022562:Salmonella Vaccines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4