Role of Toll-like receptors in host responses to a virulence antigen of Streptococcus mutans expressed by a recombinant, attenuated Salmonella vector vaccine.
In the present study, we investigated the role of Toll-like receptors (TLRs) in host responses to the saliva-binding region (SBR) of Streptococcus mutans expressed by a recombinant, attenuated Salmonella vaccine. C57BL/6 wild type (wt), TLR2-/-, TLR4-/- and MyD88-/- mice were immunized by the intranasal route on days 0, 18 and boosted on day 98 with Salmonella typhimurium BRD 509 containing a plasmid encoding SBR. Serum and saliva samples were collected throughout the experiment and assessed for antibody activity by ELISA. Evidence is provided that the induction of a serum IgG2a (Th1-type) anti-SBR antibody response involved TLR2 signaling, whereas the anti-Salmonella response involved signaling through TLR4. The adaptor molecule MyD88 was not essential for the induction of a primary Th1-type response to SBR or Salmonella, but was necessary for a secondary response to SBR. Furthermore, the absence of TLR2, TLR4 or MyD88 resulted in enhanced Th2-type serum IgG1 anti-SBR and anti-Salmonella responses. Mucosal IgA responses to SBR were TLR2-, TLR4- and MyD88-dependent, while IgA responses to Salmonella were TLR4- and MyD88-dependent.
Salam
Mohammad Abdus
MA
Department of Biomedical and Diagnostic Sciences, University of Detroit Mercy School of Dentistry, Detroit, MI 48208, United States.
Katz
Jannet
J
Michalek
Suzanne M
SM
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D012463:Saliva / Q000276:immunology; D012475:Salmonella / Q000276:immunology; D015398:Signal Transduction; D022541:Streptococcal Vaccines / Q000276:immunology*; D013295:Streptococcus mutans / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D022541:Streptococcal Vaccines; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic