Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice
Food allergy is a potentially fatal disease affecting 8% of children and has become increasingly common in the past two decades. Despite the prevalence and severe nature of the disease, the mechanisms underlying sensitization remain to be further elucidated. The Collaborative Cross is a genetically...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.599637/full |
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| author | Johanna M. Smeekens Johanna M. Smeekens Brandi T. Johnson-Weaver Andrew L. Hinton Andrew L. Hinton M. Andrea Azcarate-Peril M. Andrea Azcarate-Peril Timothy P. Moran Robert M. Immormino Janelle R. Kesselring Janelle R. Kesselring Erin C. Steinbach Kelly A. Orgel Kelly A. Orgel Herman F. Staats Herman F. Staats Herman F. Staats A. Wesley Burks A. Wesley Burks Peter J. Mucha Peter J. Mucha Martin T. Ferris Michael D. Kulis Michael D. Kulis |
| author_facet | Johanna M. Smeekens Johanna M. Smeekens Brandi T. Johnson-Weaver Andrew L. Hinton Andrew L. Hinton M. Andrea Azcarate-Peril M. Andrea Azcarate-Peril Timothy P. Moran Robert M. Immormino Janelle R. Kesselring Janelle R. Kesselring Erin C. Steinbach Kelly A. Orgel Kelly A. Orgel Herman F. Staats Herman F. Staats Herman F. Staats A. Wesley Burks A. Wesley Burks Peter J. Mucha Peter J. Mucha Martin T. Ferris Michael D. Kulis Michael D. Kulis |
| author_sort | Johanna M. Smeekens |
| collection | DOAJ |
| description | Food allergy is a potentially fatal disease affecting 8% of children and has become increasingly common in the past two decades. Despite the prevalence and severe nature of the disease, the mechanisms underlying sensitization remain to be further elucidated. The Collaborative Cross is a genetically diverse panel of inbred mice that were specifically developed to study the influence of genetics on complex diseases. Using this panel of mouse strains, we previously demonstrated CC027/GeniUnc mice, but not C3H/HeJ mice, develop peanut allergy after oral exposure to peanut in the absence of a Th2-skewing adjuvant. Here, we investigated factors associated with sensitization in CC027/GeniUnc mice following oral exposure to peanut, walnut, milk, or egg. CC027/GeniUnc mice mounted antigen-specific IgE responses to peanut, walnut and egg, but not milk, while C3H/HeJ mice were not sensitized to any antigen. Naïve CC027/GeniUnc mice had markedly lower total fecal IgA compared to C3H/HeJ, which was accompanied by stark differences in gut microbiome composition. Sensitized CC027/GeniUnc mice had significantly fewer CD3+ T cells but higher numbers of CXCR5+ B cells and T follicular helper cells in the mesenteric lymph nodes compared to C3H/HeJ mice, which is consistent with their relative immunoglobulin production. After oral challenge to the corresponding food, peanut- and walnut-sensitized CC027/GeniUnc mice experienced anaphylaxis, whereas mice exposed to milk and egg did not. Ara h 2 was detected in serum collected post-challenge from peanut-sensitized mice, indicating increased absorption of this allergen, while Bos d 5 and Gal d 2 were not detected in mice exposed to milk and egg, respectively. Machine learning on the change in gut microbiome composition as a result of food protein exposure identified a unique signature in CC027/GeniUnc mice that experienced anaphylaxis, including the depletion of Akkermansia. Overall, these results demonstrate several factors associated with enteral sensitization in CC027/GeniUnc mice, including diminished total fecal IgA, increased allergen absorption and altered gut microbiome composition. Furthermore, peanuts and tree nuts may have inherent properties distinct from milk and eggs that contribute to allergy. |
| first_indexed | 2024-12-24T05:13:22Z |
| format | Article |
| id | doaj.art-841f66418b1d4c8393bc5558dcc2038b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T05:13:22Z |
| publishDate | 2021-01-01 |
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| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-841f66418b1d4c8393bc5558dcc2038b2022-12-21T17:13:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.599637599637Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible MiceJohanna M. Smeekens0Johanna M. Smeekens1Brandi T. Johnson-Weaver2Andrew L. Hinton3Andrew L. Hinton4M. Andrea Azcarate-Peril5M. Andrea Azcarate-Peril6Timothy P. Moran7Robert M. Immormino8Janelle R. Kesselring9Janelle R. Kesselring10Erin C. Steinbach11Kelly A. Orgel12Kelly A. Orgel13Herman F. Staats14Herman F. Staats15Herman F. Staats16A. Wesley Burks17A. Wesley Burks18Peter J. Mucha19Peter J. Mucha20Martin T. Ferris21Michael D. Kulis22Michael D. Kulis23Department of Pediatrics, Division of Rheumatology, Allergy and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesUNC Food Allergy Initiative, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pathology, Duke University School of Medicine, Durham, NC, United StatesUNC Food Allergy Initiative, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesCurriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, United StatesUNC Microbiome Core, Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pediatrics, Division of Rheumatology, Allergy and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pediatrics, Division of Rheumatology, Allergy and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pediatrics, Division of Rheumatology, Allergy and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesUNC Food Allergy Initiative, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pediatrics, Division of Rheumatology, Allergy and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pediatrics, Division of Rheumatology, Allergy and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesUNC Food Allergy Initiative, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pathology, Duke University School of Medicine, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United StatesDepartment of Immunology, Duke University School of Medicine, Durham, NC, United StatesDepartment of Pediatrics, Division of Rheumatology, Allergy and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesUNC Food Allergy Initiative, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesCurriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Mathematics and Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, NC, United States0Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Pediatrics, Division of Rheumatology, Allergy and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesUNC Food Allergy Initiative, School of Medicine, University of North Carolina, Chapel Hill, NC, United StatesFood allergy is a potentially fatal disease affecting 8% of children and has become increasingly common in the past two decades. Despite the prevalence and severe nature of the disease, the mechanisms underlying sensitization remain to be further elucidated. The Collaborative Cross is a genetically diverse panel of inbred mice that were specifically developed to study the influence of genetics on complex diseases. Using this panel of mouse strains, we previously demonstrated CC027/GeniUnc mice, but not C3H/HeJ mice, develop peanut allergy after oral exposure to peanut in the absence of a Th2-skewing adjuvant. Here, we investigated factors associated with sensitization in CC027/GeniUnc mice following oral exposure to peanut, walnut, milk, or egg. CC027/GeniUnc mice mounted antigen-specific IgE responses to peanut, walnut and egg, but not milk, while C3H/HeJ mice were not sensitized to any antigen. Naïve CC027/GeniUnc mice had markedly lower total fecal IgA compared to C3H/HeJ, which was accompanied by stark differences in gut microbiome composition. Sensitized CC027/GeniUnc mice had significantly fewer CD3+ T cells but higher numbers of CXCR5+ B cells and T follicular helper cells in the mesenteric lymph nodes compared to C3H/HeJ mice, which is consistent with their relative immunoglobulin production. After oral challenge to the corresponding food, peanut- and walnut-sensitized CC027/GeniUnc mice experienced anaphylaxis, whereas mice exposed to milk and egg did not. Ara h 2 was detected in serum collected post-challenge from peanut-sensitized mice, indicating increased absorption of this allergen, while Bos d 5 and Gal d 2 were not detected in mice exposed to milk and egg, respectively. Machine learning on the change in gut microbiome composition as a result of food protein exposure identified a unique signature in CC027/GeniUnc mice that experienced anaphylaxis, including the depletion of Akkermansia. Overall, these results demonstrate several factors associated with enteral sensitization in CC027/GeniUnc mice, including diminished total fecal IgA, increased allergen absorption and altered gut microbiome composition. Furthermore, peanuts and tree nuts may have inherent properties distinct from milk and eggs that contribute to allergy.https://www.frontiersin.org/articles/10.3389/fimmu.2020.599637/fullfood allergypeanut allergyIgEmicrobiomeTfh cellsfecal IgA |
| spellingShingle | Johanna M. Smeekens Johanna M. Smeekens Brandi T. Johnson-Weaver Andrew L. Hinton Andrew L. Hinton M. Andrea Azcarate-Peril M. Andrea Azcarate-Peril Timothy P. Moran Robert M. Immormino Janelle R. Kesselring Janelle R. Kesselring Erin C. Steinbach Kelly A. Orgel Kelly A. Orgel Herman F. Staats Herman F. Staats Herman F. Staats A. Wesley Burks A. Wesley Burks Peter J. Mucha Peter J. Mucha Martin T. Ferris Michael D. Kulis Michael D. Kulis Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice Frontiers in Immunology food allergy peanut allergy IgE microbiome Tfh cells fecal IgA |
| title | Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice |
| title_full | Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice |
| title_fullStr | Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice |
| title_full_unstemmed | Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice |
| title_short | Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice |
| title_sort | fecal iga antigen absorption and gut microbiome composition are associated with food antigen sensitization in genetically susceptible mice |
| topic | food allergy peanut allergy IgE microbiome Tfh cells fecal IgA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.599637/full |
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