Toll-like receptor 2 ligands activate human basophils for both IgE-dependent and IgE-independent secretion

被引:89
作者
Bieneman, AP [1 ]
Chichester, KL [1 ]
Chen, YH [1 ]
Schroeder, JT [1 ]
机构
[1] Johns Hopkins Univ, Johns Hopkins Asthma & Allergy Ctr, Dept Med, Div Clin Immunol,Unit Off 2, Baltimore, MD 21224 USA
关键词
innate immunity; basophil; IgE; cytokines; Toll-like receptors; allergy; human;
D O I
10.1016/j.jaci.2004.10.018
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Toll-like receptor (TLR) molecules play a critical role in directing the course of acquired immunity, including that associated with allergic disease, by recognizing specific microbial products that activate immune cells for effector functions. Objective: We investigated whether human basophils express 2 such molecules (TLR2 and TLR4), and assessed whether putative ligands for these receptors activate nuclear factor kappaB (NFkappaB) and modulate mediator release and cytokine secretion either alone or in response to stimulation. Methods: Toll-like receptor expression was assessed by using RT-PCR and flow cytometry. Immunoblotting detected nuclear NFkappaB. Automated fluorometry, RIA, and ELISA detected concurrent changes in histamine, leukotriene C-4, and cytokine, respectively, after culture with specific ligands. Results: mRNA and protein for TLR2 and TLR4 were detected in basophils. However, in assessing nuclear localization of NFkappaB as a measure of functional receptor responses, basophils selectively reacted only to peptidoglyean, a TLR2 ligand, and not to LPS, a TLR4 ligand. Likewise, basophils secreted both IL-4 and IL-13 in direct response to peptidoglycan but not to LPS. Although neither ligand induced histamine or leukotriene C-4 release, several TLR2-specific ligands augmented the secretion of these mediators (and cytokine) in response to IgE-dependent activation and of IL-13 in response to IgE-independent stimulation. Finally, a selective inhibitor of NFkappaB did not prevent these enhancing effects mediated by TLR2 ligands. Conclusion: These data suggest that innate immune responses mediated through TLR2 play a role in augmenting;allergic reactions, in part by modulating basophil cytokine secretion and mediator release independently of NFkappaB activation.
引用
收藏
页码:295 / 301
页数:7
相关论文
共 30 条
[1]  
Adkinson NF, 1980, MEASUREMENT TOTAL SE
[2]   Inferences, questions and possibilities in toll-like receptor signalling [J].
Beutler, B .
NATURE, 2004, 430 (6996) :257-263
[3]   IFN-α inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release [J].
Chen, YH ;
Bieneman, AP ;
Creticos, PS ;
Chichester, KL ;
Schroeder, JT .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2003, 112 (05) :944-950
[4]   Airway peptidoglycan and immunostimulatory DNA exposures have divergent effects on the development of airway allergen hypersensitivities [J].
Chisholm, D ;
Libet, L ;
Hayashi, T ;
Horner, AA .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2004, 113 (03) :448-454
[5]   Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen [J].
Eisenbarth, SC ;
Piggott, DA ;
Huleatt, JW ;
Visintin, I ;
Herrick, CA ;
Bottomly, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (12) :1645-1651
[6]  
GILBERT HS, 1975, BLOOD, V46, P279
[7]   Innate immune recognition [J].
Janeway, CA ;
Medzhitov, R .
ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 :197-216
[8]   Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens [J].
Kadowaki, N ;
Ho, S ;
Antonenko, S ;
Malefyt, RD ;
Kastelein, RA ;
Bazan, F ;
Liu, YJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (06) :863-869
[9]   INHIBITION OF NUCLEAR TRANSLOCATION OF TRANSCRIPTION FACTOR NF-KAPPA-B BY A SYNTHETIC PEPTIDE-CONTAINING A CELL MEMBRANE-PERMEABLE MOTIF AND NUCLEAR-LOCALIZATION SEQUENCE [J].
LIN, YZ ;
YAO, SY ;
VEACH, RA ;
TORGERSON, TR ;
HAWIGER, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (24) :14255-14258
[10]   Endotoxin exposure in allergy and asthma: Reconciling a paradox [J].
Liu, AH .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2002, 109 (03) :379-392