Title (eng)

Mould allergen Alt a 1 spiked with the micronutrient retinoic acid reduces Th2 response and ameliorates Alternaria allergy in BALB/c mice

Author

Aila Fakhimahmadi   University of Veterinary Medicine Vienna / Medical University of Vienna

Karin Hufnagl   University of Veterinary Medicine Vienna / Medical University of Vienna / AllergyCare Allergy Diagnosis Center

Erika Jensen-Jarolim   University of Veterinary Medicine Vienna / Medical University of Vienna / AllergyCare Allergy Diagnosis Center / Biomedical International R+D GmbH

Isabella Pali-Schöll   University of Veterinary Medicine Vienna / Medical University of Vienna

Franziska Roth-Walter   University of Veterinary Medicine Vienna / Medical University of Vienna

Gerlinde Hofstetter   University of Veterinary Medicine Vienna

Markus Wiederstein   University of Salzburg

Sebastian A. Jensen   University of Veterinary Medicine Vienna / AllergyCare Allergy Diagnosis Center

Markus Berger   University of Veterinary Medicine Vienna

Nathalie Szepannek   University of Veterinary Medicine Vienna

Rodolfo Bianchini   University of Veterinary Medicine Vienna

Publishing

Wiley

Description (eng)

We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo.Alt a 1-RA complex formation was analyzed in silico and in vitro. PBMCs from Alternaria-allergic donors were stimulated with Alt a 1 complexed with RA (holo-Alt a 1) or empty apo-Alt a 1 and analyzed for cytokine production and CD marker expression. Serum IgE-binding and crosslinking assays to apo- and holo-protein were correlated to B-cell epitope analysis. Female BALB/c mice already sensitized to Alt a 1 were intranasally treated with apo-Alt a 1, holo-Alt a 1 or RA alone before measuring anaphylactic response, serum antibody levels, splenic cytokines and CD marker expression.In silico docking calculations and in vitro assays showed that the extent of RA binding depended on the higher quaternary state of Alt a 1. Holo-Alt a 1 loaded with RA reduced IL-13 released from PBMCs and CD3+CD4+CRTh2 cells. Complexing Alt a 1 to RA masked its IgE B-cell epitopes and reduced its IgE-binding capacity. In a therapeutic mouse model of Alternaria allergy nasal application of holo-Alt a 1, but not of apo-Alt a 1, significantly impeded the anaphylactic response, impaired splenic antigen-presenting cells and induced IL-10 production.Holo-Alt a 1 binding to RA was able to alleviate Th2 immunity in vitro, modulate an ongoing Th2 response and prevent anaphylactic symptoms in vivo, presenting a novel option for improving allergen-specific immunotherapy in Alternaria allergy.

Object languages

English

Date

2024

Rights

This work is licensed under a
CC BY-NC 4.0 - Creative Commons Attribution-NonCommercial 4.0 International License.

CC BY-NC 4.0 International

http://creativecommons.org/licenses/by-nc/4.0/

Classification

Alternaria Alternata; Fungal Allergy; Immunomodulation; Retinoic Acid; Vitamin A

Member of the Collection(s) (1)