Secretory protein beta-lactoglobulin in cattle stable dust may contribute to the allergy-protective farm effect

Pali-Schöll, Isabella and Bianchini, Rodolfo and Afify, Sheriene Moussa and Hofstetter, Gerlinde and Winkler, Simona and Ahlers, Stella and Altemeier, Theresa and Mayerhofer, Hanna and Hufnagl, Karin and Korath, Anna D. J. and Pranger, Christina and Widhalm, Raimund and Hann, Stephan and Wittek, Thomas and Kasper-Giebl, Anne and Pacios, Luis F. and Roth-Walter, Franziska and Vercelli, Donata and von Mutius, Erika and Jensen-Jarolim, Erika

Clinical and Translational Allergy

2022

12

2

e12125

BLG, cattle, farm effect, immunomodulation, stable, zinc

https://doi.org/10.1002/clt2.12125

https://onlinelibrary.wiley.com/doi/pdf/10.1002/clt2.12125

Abstract Background Growing up on a cattle farm and consuming raw cow's milk protects against asthma and allergies. We expect a cattle-specific protein as active component in this farm effect. Methods Dust was collected from cattle and poultry stables and from mattresses of households. Urine was obtained from cattle, and ambient aerosols were sampled. Samples were analysed for BLG by SDS PAGE/immunoblot and mass spectrometry, and for association with metals by SEC-ICP-MS. PBMC of healthy donors were incubated with BLG +/− zinc, and proliferation and cytokines determined. BALB/c mice were pre-treated intranasally with stable dust extract containing BLG or depleted of BLG, and subsequent allergy response after sensitization was evaluated on antibody and symptom level. Results A major protein in dust from cattle farms and ambient air was identified as BLG. Urine from female and male cattle is a major source of BLG. In dust samples, BLG was associated with zinc. In vitro, zinc-BLG provoked significantly lower proliferation of CD4+ and CD8+ cells while inducing significantly higher levels of IFN-γ and IL-6 than the apo-BLG devoid of zinc. In vivo, pre-treatment of mice with dust extract containing BLG resulted in lower allergy symptom scores to BLG and unrelated Bet v 1 than pre-treatment with extract depleted of BLG. These in vitro and in vivo effects were independent of endotoxin. Conclusion The lipocalin BLG is found in large amounts in cattle urine, accumulates in bovine dust samples and is aerosolized around farms. Its association with zinc favorably shapes the human cellular immune response towards Th1-cytokines in vitro. BLG together with zinc in stable dust protects mice from allergic sensitization. BLG with its associated ligands may in an innate manner contribute to the allergy-protective farm effect.