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Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice
Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464972/ https://www.ncbi.nlm.nih.gov/pubmed/36105216 http://dx.doi.org/10.3389/fphar.2022.833380 |
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author | Goldblatt, David L. Valverde Ha, Gabriella Wali, Shradha Kulkarni, Vikram V. Longmire, Michael K. Jaramillo, Ana M. Chittuluru, Rosha P. Fouts, Adrienne Martinez-Moczygemba, Margarita Lei, Jonathan T. Huston, David P. Tuvim, Michael J. Dickey, Burton F. Evans, Scott E. |
author_facet | Goldblatt, David L. Valverde Ha, Gabriella Wali, Shradha Kulkarni, Vikram V. Longmire, Michael K. Jaramillo, Ana M. Chittuluru, Rosha P. Fouts, Adrienne Martinez-Moczygemba, Margarita Lei, Jonathan T. Huston, David P. Tuvim, Michael J. Dickey, Burton F. Evans, Scott E. |
author_sort | Goldblatt, David L. |
collection | PubMed |
description | Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells can sense allergens via expression of myriad Toll-like receptors (TLRs) and other pattern-recognition receptors. We sought to determine whether the innate immune response stimulated by a combination of Pam2CSK4 (“Pam2”, TLR2/6 ligand) and a class C oligodeoxynucleotide ODN362 (“ODN”, TLR9 ligand), when delivered together by aerosol (“Pam2ODN”), can modulate the allergic immune response to allergens. Treatment with Pam2ODN 7 days before sensitization to House Dust Mite (HDM) extract resulted in a strong reduction in eosinophilic and lymphocytic inflammation. This Pam2ODN immunomodulatory effect was also seen using Ovalbumin (OVA) and A. oryzae (Ao) mouse models. The immunomodulatory effect was observed as much as 30 days before sensitization to HDM, but ineffective just 2 days after sensitization, suggesting that Pam2ODN immunomodulation lowers the allergic responsiveness of the lung, and reduces the likelihood of inappropriate sensitization to aeroallergens. Furthermore, Pam2 and ODN cooperated synergistically suggesting that this treatment is superior to any single agonist in the setting of allergen immunotherapy. |
format | Online Article Text |
id | pubmed-9464972 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94649722022-09-13 Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice Goldblatt, David L. Valverde Ha, Gabriella Wali, Shradha Kulkarni, Vikram V. Longmire, Michael K. Jaramillo, Ana M. Chittuluru, Rosha P. Fouts, Adrienne Martinez-Moczygemba, Margarita Lei, Jonathan T. Huston, David P. Tuvim, Michael J. Dickey, Burton F. Evans, Scott E. Front Pharmacol Pharmacology Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells can sense allergens via expression of myriad Toll-like receptors (TLRs) and other pattern-recognition receptors. We sought to determine whether the innate immune response stimulated by a combination of Pam2CSK4 (“Pam2”, TLR2/6 ligand) and a class C oligodeoxynucleotide ODN362 (“ODN”, TLR9 ligand), when delivered together by aerosol (“Pam2ODN”), can modulate the allergic immune response to allergens. Treatment with Pam2ODN 7 days before sensitization to House Dust Mite (HDM) extract resulted in a strong reduction in eosinophilic and lymphocytic inflammation. This Pam2ODN immunomodulatory effect was also seen using Ovalbumin (OVA) and A. oryzae (Ao) mouse models. The immunomodulatory effect was observed as much as 30 days before sensitization to HDM, but ineffective just 2 days after sensitization, suggesting that Pam2ODN immunomodulation lowers the allergic responsiveness of the lung, and reduces the likelihood of inappropriate sensitization to aeroallergens. Furthermore, Pam2 and ODN cooperated synergistically suggesting that this treatment is superior to any single agonist in the setting of allergen immunotherapy. Frontiers Media S.A. 2022-08-29 /pmc/articles/PMC9464972/ /pubmed/36105216 http://dx.doi.org/10.3389/fphar.2022.833380 Text en Copyright © 2022 Goldblatt, Valverde Ha, Wali, Kulkarni, Longmire, Jaramillo, Chittuluru, Fouts, Martinez-Moczygemba, Lei, Huston, Tuvim, Dickey and Evans. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Goldblatt, David L. Valverde Ha, Gabriella Wali, Shradha Kulkarni, Vikram V. Longmire, Michael K. Jaramillo, Ana M. Chittuluru, Rosha P. Fouts, Adrienne Martinez-Moczygemba, Margarita Lei, Jonathan T. Huston, David P. Tuvim, Michael J. Dickey, Burton F. Evans, Scott E. Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice |
title | Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice |
title_full | Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice |
title_fullStr | Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice |
title_full_unstemmed | Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice |
title_short | Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice |
title_sort | epithelial immunomodulation by aerosolized toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464972/ https://www.ncbi.nlm.nih.gov/pubmed/36105216 http://dx.doi.org/10.3389/fphar.2022.833380 |
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