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

Anja P. Bieneman, Kristin L. Chichester, Yi Hsing Chen, John T. Schroeder

Research output: Contribution to journalArticlepeer-review

Abstract

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 κB (NFκB) 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 NFκB. Automated fluorometry, RIA, and ELISA detected concurrent changes in histamine, leukotriene C4, 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 NFκB as a measure of functional receptor responses, basophils selectively reacted only to peptidoglycan, 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 NFκB 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 NFκB activation.

Original languageEnglish (US)
Pages (from-to)295-301
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume115
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • Allergy
  • Basophil
  • Cytokines
  • Human
  • IgE
  • Innate immunity
  • Toll-like receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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