The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency.
- Author:
Kyung Tae NOH
1
;
Sung Jae SHIN
;
Kwang Hee SON
;
In Duk JUNG
;
Hyun Kyu KANG
;
Su Jung LEE
;
Eun Kyung LEE
;
Yong Kyoo SHIN
;
Ji Chang YOU
;
Yeong Min PARK
Author Information
1. Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan 626-870, Korea. immunpym@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
dendritic cells;
FAP-A protein, Mycobacterium avium;
glycogen synthase kinase-3;
toll-like receptor 4
- MeSH:
*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
- From:Experimental & Molecular Medicine
2012;44(5):340-349
- CountryRepublic of Korea
- Language:English
-
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.
