1. Bovine Holo-Beta-Lactoglobulin Cross-Protects Against Pollen Allergies in an Innate Manner in BALB/c Mice: Potential Model for the Farm Effect.
- Author
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Afify SM, Pali-Schöll I, Hufnagl K, Hofstetter G, El-Bassuoni MA, Roth-Walter F, and Jensen-Jarolim E
- Subjects
- Administration, Intranasal, Animals, Antibody Specificity, Antigen Presentation immunology, Cattle, Cytokines metabolism, Female, Immunization, Passive, Immunoglobulin E immunology, Immunoglobulin G blood, Immunoglobulin G immunology, Lactoglobulins administration & dosage, Mice, Pollen adverse effects, Th2 Cells immunology, Th2 Cells metabolism, Allergens immunology, Cross Protection immunology, Lactoglobulins immunology, Pollen immunology, Rhinitis, Allergic, Seasonal immunology, Rhinitis, Allergic, Seasonal prevention & control
- Abstract
The lipocalin beta-lactoglobulin (BLG) is a major protein compound in cow's milk, and we detected it in cattle stable dust. BLG may be a novel player in the farm protective effect against atopic sensitization and hayfever. In previous studies, we demonstrated that only the ligand-filled holo-form of BLG prevented sensitization to itself. Here, we investigated whether holo-BLG could, in an innate manner, also protect against allergic sensitization to unrelated birch pollen allergens using a murine model. BALB/c mice were nasally pretreated four times in biweekly intervals with holo-BLG containing quercetin-iron complexes as ligands, with empty apo-BLG, or were sham-treated. Subsequently, mice were intraperitoneally sensitized two times with apo-BLG or with the unrelated birch pollen allergen apo-Bet v 1, adjuvanted with aluminum hydroxide. After subsequent systemic challenge with BLG or Bet v 1, body temperature drop was monitored by anaphylaxis imaging. Specific antibodies in serum and cytokines of BLG- and Bet v 1-stimulated splenocytes were analyzed by ELISA. Additionally, human peripheral blood mononuclear cells of pollen allergic subjects were stimulated with apo- versus holo-BLG before assessment by FACS. Prophylactic treatment with the holo-BLG resulted in protection against allergic sensitization and clinical reactivity also to Bet v 1 in an unspecific manner. Pretreatment with holo-BLG resulted in significantly lower BLG-as well as Bet v 1-specific antibodies and impaired antigen-presentation with significantly lower numbers of CD11c+MHCII+ cells expressing CD86. Pretreatment with holo-BLG also reduced the release of Th2-associated cytokines from Splenocytes in BLG-sensitized mice. Similarly, in vitro stimulation of PBMCs from birch pollen allergic subjects with holo-BLG resulted in a relative decrease of CD3+CD4+ and CD4+CRTh2 cells, but not of CD4+CD25+CD127- Treg cells, compared to apo-BLG stimulation. In conclusion, prophylactic treatment with holo-BLG protected against allergy in an antigen-specific and -unspecific manner by decreasing antigen presentation, specific antibody production and abrogating a Th2-response. Holo-BLG therefore promotes immune resilience against pollen allergens in an innate manner and may thereby contribute to the farm protective effect against atopic sensitization., Competing Interests: EJ-J is a shareholder of Biomedical International R+D GmbH, Vienna, Austria. EJ-J and FR-W are inventors of EP2894478, LCN2 as a tool for allergy diagnostic and therapy. EP 14150965.3, Year: 01/2014; US 14/204,570, owned by Biomedical International R+D GmbH, Vienna, Austria. The authors declare that this study received funding from Biomedical International R+D GmbH, Vienna, Austria and Bencard Allergy GmbH, Germany. Both funders provided research grants for the laboratory work and employment of S.M.A. as PhD student. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Afify, Pali-Schöll, Hufnagl, Hofstetter, El-Bassuoni, Roth-Walter and Jensen-Jarolim.)
- Published
- 2021
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