Dendritic cells stimulated with outer membrane protein A (OmpA) of Salmonella typhimurium generate effective anti-tumor immunity
Abstract Gram-negative bacterial outer membrane proteins (Omps) have an important role in pathogenesis and signal reception. We previously reported that Acinetobacter OmpA ( Ab OmpA) induced maturation of bone marrow-derived dendritic cells (BMDCs) and that Ab OmpA-primed DCs produced IL-12 which ge...
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Published in | Vaccine Vol. 29; no. 13; pp. 2400 - 2410 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English French |
Published |
Kidlington
Elsevier Ltd
16.03.2011
Elsevier Elsevier Limited |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract Gram-negative bacterial outer membrane proteins (Omps) have an important role in pathogenesis and signal reception. We previously reported that Acinetobacter OmpA ( Ab OmpA) induced maturation of bone marrow-derived dendritic cells (BMDCs) and that Ab OmpA-primed DCs produced IL-12 which generated Th1 CD4+ T-cells. We analyzed the effects of Salmonella typhimurium OmpA (OmpA-Sal) on dendritic cell (DC) maturation in the present study, and determined that tumor antigen-pulsed DCs stimulated with OmpA-Sal induced anti-tumor responses in a mouse model. OmpA-Sal activated BMDCs by augmenting expression of MHC class II and of the co-stimulatory molecules CD80 and CD86. RT-PCR revealed that IL-12(p40) gene expression is highly augmented in OmpA-Sal-stimulated BMDCs. DNA (CRT/E7) vaccination combined with OmpA-Sal stimulation generated more antigen-specific CD8+ T-cells in the present study. Certain antigen-pulsed BMDCs stimulated with OmpA-Sal induced strong PADRE-specific CD4+ and E7-specific CD8+ T-cell responses. In addition, BMDCs stimulated with OmpA-Sal (OmpA-Sal-BMDCs) and pulsed with both E7 and PADRE peptide generated greater numbers of E7-specific CD8+ effector and memory T-cells than those pulsed with E7 peptide alone. E7- and PADRE-expressing OmpA-Sal-BMDC vaccines resulted in significant long-term protective anti-tumor effects in vaccinated mice. Our data suggested that E7- and PADRE-expressing BMDCs that were matured in the presence of OmpA-Sal might enhance anti-tumor immunity and support the therapeutic use of OmpA-Sal in DC-based immunotherapy. |
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Bibliography: | http://dx.doi.org/10.1016/j.vaccine.2011.01.036 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0264-410X 1873-2518 |
DOI: | 10.1016/j.vaccine.2011.01.036 |