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KMID : 0620920120440050340
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Experimental & Molecular Medicine
2012 Volume.44 No. 5 p.340 ~ p.349
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The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency
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Noh Kyung-Tae
Shin Sung-Jae
Son Kwang-Hee
Jung In-Duk
Kang Hyun-Kyu
Lee Su-Jung
Lee Eun-Kyung
Shin Yong-Kyoo
You Ji-Chang
Park Yeong-Min
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Abstract
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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.
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KEYWORD
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dendritic cells, FAP-A protein, Mycobacterium avium, glycogen synthase kinase-3, toll-like receptor 4
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