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Details

Autor(en) / Beteiligte
Titel
Mast cell-mediated immune responses through IgE antibody and Toll-like receptor 4 by malarial peroxiredoxin
Ist Teil von
  • European journal of immunology, 2008-05, Vol.38 (5), p.1341-1350
Ort / Verlag
Weinheim: Wiley-VCH Verlag
Erscheinungsjahr
2008
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
  • In this study, 2-Cys Plasmodium berghei ANKA (PbA) peroxiredoxin (Prx) was identified as an antigenic protein recognized by an anti-PbA IgE antibody using two-dimensional polyacrylamide gel electrophoresis and proteomic analysis. Innate immune responses to PbAPrx were examined using cells from mice deficient in Toll-like receptors (TLR) or related molecules, and it was demonstrated that responses were severely impaired in TLR4⁻/⁻, MyD88⁻/⁻ and MD-2⁻/⁻ mice, but not in Toll/IL-1 receptor domain-containing adaptor inducing IFN-γ (TRIF)⁻/⁻, TLR2⁻/⁻ or radioprotective 105 (RP105)⁻/⁻ mice. An association between PbAPrx and TLR4 was observed following immunoprecipitation and immunoblotting, suggesting that PbAPrx was associated with TLR4/MD-2. Interactions between Prx and TLR4/MD-2 were also examined by flow cytometry using TLR4/MD-2- or TLR2-expressing cells. NFκB/GFP activity was observed in TLR4/MD-2- but not in TLR2-expressing cells following stimulation with Prx. However, this effect was not observed after treatment with proteinase K, suggesting that PbAPrx is a protein ligand for TLR4 and that the PbAPrx activity observed in this study is not due to contamination with LPS. These findings indicate that malarial Prx induces IgE-mediated protection through FcεRI on mast cells and innate immunity through TLR4 with MyD88 and MD-2, suggesting a novel function for malarial Prx in innate and acquired immune responses in malaria.

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