title: Contribution of a Streptococcus mutans antigen expressed by a Salmonella vector vaccine in dendritic cell activation.
abstract: A Salmonella vector vaccine expressing the saliva-binding region (SBR) of the adhesin AgI/II of Streptococcus mutans has been shown to induce a mixed Th1/Th2 anti-SBR immune response in mice and to require Toll-like receptor 2 (TLR2), TLR4, and MyD88 signaling for the induction of mucosal anti-SBR antibody responses. Since dendritic cells (DC) are critical in innate and adaptive immunity, the present study assessed the role of SBR expression by the vector vaccine in DC activation. Bone marrow-derived DC from wild-type and TLR2, TLR4, and MyD88 knockout mice were stimulated with Salmonella vector BRD509, the SBR-expressing Salmonella vector vaccine BRD509(pSBRT7), or SBR protein, and the DC responses to different stimuli were compared by assessing costimulatory molecule expression, cytokine production, and signaling pathways. The DC response to both BRD509(pSBRT7) and BRD509 was dependent mainly on TLR4. BRD509(pSBRT7) and BRD509 induced upregulation of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) expression. Lower levels of interleukin-10 (IL-10) and IL-12p40 were produced by BRD509(pSBRT7)-stimulated DC than by BRD509-stimulated DC. Furthermore, BRD509(pSBRT7)-stimulated DC showed decreased p38 phosphorylation compared to that induced by DC stimulated with BRD509. However, BRD509(pSBRT7)-treated DC produced a higher level of IL-6 than BRD509-stimulated cells. The low IL-12p40 and high IL-6 cytokine profile expressed by BRD509(pSBRT7)-stimulated DC may represent a shift toward a Th2 response, as suggested by the increased expression in Jagged-1. These results provide novel evidence that a heterologous protein expressed by a Salmonella vector vaccine can differentially affect DC activation.
authors: Department of Microbiology, University of Alabama at Birmingham, 845 South 19th Street, BBRB 258/5, Birmingham, AL 35294-2170, USA.
authors: Qingan
authors: Q
authors: Xu
authors: Jenny
authors: J
authors: Katz
authors: Ping
authors: P
authors: Zhang
authors: Amit R
authors: AR
authors: Ashtekar
authors: Dalia E
authors: DE
authors: Gaddis
authors: Mingwen
authors: M
authors: Fan
authors: Suzanne M
authors: SM
authors: Michalek
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000276:immunology*; D019013:CD40 Antigens / Q000096:biosynthesis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005802:Genes, MHC Class II; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D010766:Phosphorylation; D019779:Salmonella enterica / Q000235:genetics / Q000276:immunology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D022541:Streptococcal Vaccines; D013295:Streptococcus mutans / Q000235:genetics / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001426:Bacterial Proteins; D019013:CD40 Antigens; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D000072099:Serrate-Jagged Proteins; D022541:Streptococcal Vaccines; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C045564:saliva-interacting cell wall protein, Streptococcus; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases