Suchergebnisse

TLRs directly induce innate host defense responses, but the mechanisms of TLR-mediated adaptive immunity remain subject to debate. In this study, we clarified a role of TLR-mediated innate immunity for induction of adaptive immunity by oral vaccination with a live recombinant attenuated Salmonella enteric serovar Typhimurium vaccine (RASV) strain expressing Streptococcus pneumoniae surface protein A (PspA) Ag. Of note, oral or intranasal vaccination with RASV expressing PspA resulted in identical or even significantly higher levels of PspA-specific IgG and IgA responses in the systemic and mucosal compartments of MyD88–/– mice of either BALB/c or C57BL/6 background when compared with those of wild-type mice. Although PspA-specific CD4+ T cell proliferation in the MyD88–/– mice was minimal, depletion of CD4+ T cells abolished PspA-specific IgG and IgA responses in the MyD88–/– mice of BALB/c background. Of the greatest interest, MyD88–/– mice that possessed high levels of PspA-specific IgG and IgA responses but minimal levels of CD4+ T cell responses died earlier than nonvaccinated and vaccinated wild-type mice following i.v. or intranasal challenge with virulent S. pneumoniae. Taken together, these results suggest that innate immunity activated by MyD88 signals might not be necessary for Ag-specific Ab induction in both systemic and mucosal sites but is critical for protection following oral vaccination with attenuated Salmonella expressing PspA. ; This work was supported by the governments of the Republic of Korea, Sweden, and Kuwait; the Bill & Melinda Gates Foundation; National Institutes of Health Grant R01- AI056289; and by a Korea Science and Engineering Foundation (KOSEF) grant funded by the government of Korea (MEST) (Nos. 2007-04213 and R01-2008-000-10649-0).