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)
|