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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.
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.
- Source :
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Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Nov 01; Vol. 181 (9), pp. 6447-55. - Publication Year :
- 2008
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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.
- Subjects :
- Administration, Oral
Adoptive Transfer
Animals
Antibodies, Viral biosynthesis
Antibodies, Viral physiology
B-Lymphocyte Subsets microbiology
B-Lymphocyte Subsets transplantation
Bacterial Proteins biosynthesis
Bacterial Proteins immunology
Female
Immunity, Innate genetics
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88 deficiency
Myeloid Differentiation Factor 88 genetics
Pneumococcal Infections immunology
Pneumococcal Infections metabolism
Salmonella Vaccines administration & dosage
Salmonella Vaccines genetics
Signal Transduction genetics
Streptococcus pneumoniae pathogenicity
Toll-Like Receptors agonists
Toll-Like Receptors physiology
Vaccines, Attenuated administration & dosage
Vaccines, Attenuated genetics
Vaccines, Attenuated immunology
B-Lymphocyte Subsets immunology
Bacterial Proteins genetics
Epitopes, B-Lymphocyte immunology
Myeloid Differentiation Factor 88 physiology
Pneumococcal Infections prevention & control
Salmonella Vaccines immunology
Signal Transduction immunology
Streptococcus pneumoniae immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 181
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18941235
- Full Text :
- https://doi.org/10.4049/jimmunol.181.9.6447