MyD88 Signaling Is Not Essential for Induction of Antigen-Specific B Cell Responses but Is Indispensable for Protection against Streptococcus pneumoniae Infection following Oral Vaccination with Attenuated Salmonella Expressing PspA Antigen

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Park, Sung-Moo; Ko, Hyun-Jeong; Shim, Doo-Hee; Yang, Jin-Young; Park, Yong Ho; III, Roy Curtiss; Kweon, Mi-Na
Issue Date
American Association of Immunologists
J. Immunol. 181: 6447-6455
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.
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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