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.

Abstract

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.

• Authors: Sung-Moo Park, Hyun-Jeong Ko, Doo-Hee Shim, Jin-Young Yang, Yong-Ho Park, Roy Curtiss 3rd, Mi-Na Kweon
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 181 Issue 9 Pg. 6447-55 (Nov 01 2008) ISSN: 1550-6606 [Electronic] United States
• PMID: 18941235 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Bacterial Proteins
• Epitopes, B-Lymphocyte
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• Salmonella Vaccines
• Toll-Like Receptors
• Vaccines, Attenuated
• pneumococcal surface protein A

Topics

• Administration, Oral
• Adoptive Transfer
• Animals
• Antibodies, Viral (biosynthesis, physiology)
• B-Lymphocyte Subsets (immunology, microbiology, transplantation)
• Bacterial Proteins (biosynthesis, genetics, immunology)
• Epitopes, B-Lymphocyte (immunology)
• Female
• Immunity, Innate (genetics)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Differentiation Factor 88 (deficiency, genetics, physiology)
• Pneumococcal Infections (immunology, metabolism, prevention & control)
• Salmonella Vaccines (administration & dosage, genetics, immunology)
• Signal Transduction (genetics, immunology)
• Streptococcus pneumoniae (immunology, pathogenicity)
• Toll-Like Receptors (agonists, physiology)
• Vaccines, Attenuated (administration & dosage, genetics, immunology)