Exp Mol Med.
2012 May;44(5):340-349.
The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency
- Affiliations
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- 1Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan 626-870, Korea. immunpym@pusan.ac.kr
- 2Research Institute of Convergence of Biomedical Science and Technology, Pusan National University, Yangsan 626-770, Korea.
- 3Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, Korea.
- 4Department of Microbiology, Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 120-752, Korea.
- 5Yongsan Hospital College of Medicine, Chung-Ang University, Seoul 140-757, Korea.
- 6Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea.
- 7National Research Laboratory of Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Abstract
- In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and anti-inflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4+/+ BMDCs was not observed in TLR4-/- BMDCs. Furthermore, FAP induced DC-mediated CD8+ T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway.
Keyword
MeSH Terms
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*Adhesins, Bacterial/genetics/metabolism
Animals
CD8-Positive T-Lymphocytes/metabolism
*Cancer Vaccines/therapeutic use
Cell Proliferation
Cytokines/metabolism
Dendritic Cells/*cytology
Disease Models, Animal
Gene Expression Regulation
Glycogen Synthase Kinase 3/metabolism
Humans
Mice
Mice, Inbred C57BL
Mycobacterium avium/genetics/metabolism
Paratuberculosis/metabolism
Protein Binding
Signal Transduction
T-Lymphocytes, Cytotoxic/metabolism
*Thymoma/genetics/metabolism
*Toll-Like Receptor 4/agonists/genetics/metabolism
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