The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function

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dc.contributor.author Hamilton, Clare M.
dc.contributor.author Dowling, David J.
dc.contributor.author Loscher, Christine E.
dc.contributor.author Morphew, Russell M.
dc.contributor.author Brophy, Peter M.
dc.contributor.author O'Neill, Sandra M.
dc.date.accessioned 2010-03-17T10:01:21Z
dc.date.available 2010-03-17T10:01:21Z
dc.date.issued 2009-06-01
dc.identifier.citation Hamilton , C M , Dowling , D J , Loscher , C E , Morphew , R M , Brophy , P M & O'Neill , S M 2009 , ' The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function ' Infection and Immunity , vol 77 , no. 6 , pp. 2488-2498 . en
dc.identifier.issn 1098-5522
dc.identifier.other PURE: 148458
dc.identifier.other dspace: 2160/4457
dc.identifier.uri http://hdl.handle.net/2160/4457
dc.description Hamilton, C. M., Dowling, D. J., Loscher, C. E., Morphew, R. M., Brophy, P. M., O'Neill, S. M. (2009). The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function. Infection and Immunity, 77, (6), 2488-2498. Sponsorship: Dublin City University Faculty of Science and Health Targeted Research Development Fund, European Union (DELIVER) (grant FOOD-CT-2005-023025), and BBSRC (grant BB/C503638/2. Fasciola hepatica causes major economic and welfare issues to the livestock industry worldwide. Parasitic worms have been reported to suppress antigen-specific Th1 responses in concurrent bacterial infections. For the first time this paper showed that isolated antigens from F. hepatica tegument inhibited the activity of dendritic cells. The work increased molecular understanding of host-parasite and provided a platform to development novel immune therapeutics for the treatment of Th1-mediated inflammatory diseases. Contributed to experimental design (25%) and manuscript preparation (20%) and grant holder in UK on work completed as part of the EU DELIVER programme on liver fluke control. IMPF: 04.20 en
dc.description.abstract Parasitic worms and molecules derived from them have powerful anti-inflammatory properties and are shown to have therapeutic effects on inflammatory diseases. The helminth Fasciola hepatica has been reported to suppress antigen-specific Th1 responses in concurrent bacterial infections, thus demonstrating its anti-inflammatory ability in vivo. Here, F. hepatica tegumental antigen (Teg) was shown to significantly suppress serum levels of gamma interferon (IFN-) and interleukin-12p70 (IL-12p70) in a model of septic shock. Since dendritic cells (DCs) are a good source of IL-12p70 and critical in driving adaptive immunity, we investigated the effects of F. hepatica Teg on the activation and function of murine DCs. While Teg alone did not induce cytokine production or cell surface marker expression on DCs, it significantly suppressed cytokine production (IL-12p70, IL-6, IL-10, tumor necrosis factor alpha, and nitrite) and cell surface marker expression (CD80, CD86, and CD40) in DCs matured with a range of Toll-like receptor (TLR) and non-TLR ligands. Teg works independently of the TLR4 pathway, since it still functioned in DCs generated from TLR4 mutant and knockout mice. It impaired DC function by inhibiting their phagocytic capacity and their ability to prime T cells. It does not appear to target the common components (extracellular signal-regulated kinase, Jun N-terminal protein kinase, or p38) of the TLR pathways; however, it suppressed the active p65 subunit of the transcription factor NF-B in mature DCs, which could explain the impairment of proinflammatory cytokine production. Overall, our results demonstrate the potent anti-inflammatory properties of F. hepatica Teg and its therapeutic potential as an anti-inflammatory agent. en
dc.format.extent 11 en
dc.language.iso eng
dc.relation.ispartof Infection and Immunity en
dc.title The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1128/IAI.00919-08
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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