A fusion protein of flagellin and ovalbumin suppresses the TH2 response and prevents murine intestinal allergy

Stefan Schülke, Manja Burggraf, Zoe Waibler, Andrea Wangorsch, Sonja Wolfheimer, Ulrich Kalinke, Stefan Vieths, Masako Toda, Stephan Scheurer

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Background: The Toll-like receptor (TLR) 5 agonist flagellin is associated with immunomodulatory functions. Objective: We sought to investigate whether Listeria monocytogenes-derived flagellin A (flaA) can modulate ovalbumin (OVA)-specific T-cell responses and prevent OVA-induced intestinal allergy. Methods: Bone marrow-derived myeloid dendritic cells from BALB/c, C57BL/6, or TLR signaling-deficient (MyD88-/-) mice were stimulated with rOVA, rflaA, rflaA plus rOVA, or a recombinant fusion protein consisting of rflaA and rOVA (rflaA:OVA). The immunomodulating properties of rflaA plus rOVA and rflaA:OVA were investigated by means of DC-T-cell coculture with CD4+ T cells from OVA-T-cell receptor transgenic or OVA/alum-immunized mice. rflaA:OVA was applied as a prophylactic and therapeutic vaccine in a murine model of intestinal allergy. Results: rflaA:OVA induced upregulation of TLR5 and dose-dependent IL-6 and IL-10 secretion by myeloid dendritic cells. IL-10 contributed to repressing IL-4 and IFN-γ secretion by OVA-T-cell receptor transgenic CD4+ T cells. Moreover, rflaA:OVA suppressed CD4 + T cells derived from TH2-biased mice on OVA/alum immunization. In a murine model of intestinal allergy, prophylactic vaccination with rflaA:OVA reduced T-cell activation. Protection from intestinal allergy included suppression of OVA-specific IgE while inducing OVA-specific IgG 2a. Equimolar amounts of rflaA or rOVA provided alone or as a mixture did not have comparable effects. Moreover, therapeutic vaccination was shown to reduce allergic symptoms and T-cell activation in the spleen. Conclusion: The rflaA:OVA fusion protein showed strong TLR-mediated immunomodulating capacities probably attributed by the proximity of adjuvant and allergen, leading to the prevention of intestinal allergy in a murine disease model. Therefore recombinant flaA:allergen fusion proteins are promising vaccine candidates for intervention in patients with IgE-mediated allergy.

Original languageEnglish
Pages (from-to)1340-1348.e12
JournalJournal of Allergy and Clinical Immunology
Volume128
Issue number6
DOIs
Publication statusPublished - 2011 Dec
Externally publishedYes

Keywords

  • Flagellin
  • Toll-like receptor 5
  • allergen vaccine
  • dendritic cell
  • intestinal allergy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'A fusion protein of flagellin and ovalbumin suppresses the T<sub>H</sub>2 response and prevents murine intestinal allergy'. Together they form a unique fingerprint.

Cite this