Mast cell-mediated immune responses through IgE antibody and Toll-like receptor 4 by malarial peroxiredoxin.
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-gamma (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. NFkappaB/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 FcepsilonRI 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.
Furuta
Takahisa
T
Division of Infectious Genetics, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. furuta@ims.u-tokyo.ac.jp
Imajo-Ohmi
Shinobu
S
Fukuda
Hiroyuki
H
Kano
Shigeyuki
S
Miyake
Kensuke
K
Watanabe
Naohiro
N
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D051218:Lymphocyte Antigen 96 / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008288:Malaria / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D054464:Peroxiredoxins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D010962:Plasmodium berghei / Q000276:immunology; D011485:Protein Binding; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000502:physiology*; D014162:Transfection
D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; C477005:2-Cys peroxiredoxin, Plasmodium falciparum; D054464:Peroxiredoxins