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Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations
- Source :
- J Allergy Clin Immunol
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Background The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis. However, the immunologic mechanism of this strain’s susceptibility is not known. Objective We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious Toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain because both genes have been associated with food allergy. Methods We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged them with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome, and biomarkers of gut permeability. Results In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis after oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring Tlr4 or Dock8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice compared to C57BL/6 mice, which correlated with an increased number of goblet cells in the small intestine. Conclusions Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens; it also indicates that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.
- Subjects :
- Male
Arachis
Lipopolysaccharide
Immunology
Peanut allergy
Administration, Oral
Article
Permeability
chemistry.chemical_compound
Species Specificity
Food allergy
medicine
Humans
Animals
Guanine Nucleotide Exchange Factors
Immunology and Allergy
Genetic Predisposition to Disease
Peanut Hypersensitivity
Intestinal Mucosa
Anaphylaxis
Sensitization
Mice, Inbred C3H
biology
business.industry
Passive Cutaneous Anaphylaxis
Immunoglobulin E
medicine.disease
Small intestine
Gastrointestinal Microbiome
Mice, Inbred C57BL
Toll-Like Receptor 4
Disease Models, Animal
Ovalbumin
medicine.anatomical_structure
chemistry
Mutation
TLR4
biology.protein
Female
business
Food Hypersensitivity
Subjects
Details
- ISSN :
- 00916749
- Volume :
- 149
- Database :
- OpenAIRE
- Journal :
- Journal of Allergy and Clinical Immunology
- Accession number :
- edsair.doi.dedup.....009b11dda69d25c18d5d4cdfa96afb1d