Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 9, Pages 6447-6455Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.9.6447
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Funding
- Bill & Melinda Gates Foundation
- National Institutes of Health [R01-A1056299]
- Korea Science and Engineering Foundation (KOSEF)
- (MEST) [2007-04213, R01-2008-000-10649-0]
- National Research Foundation of Korea [2007-04213, R01-2008-000-10649-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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. The Journal of Immunology, 2008, 181: 6447-6455.
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