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...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.833380/full |
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| author | David L. Goldblatt David L. Goldblatt David L. Goldblatt Gabriella Valverde Ha Shradha Wali Vikram V. Kulkarni Michael K. Longmire Ana M. Jaramillo Rosha P. Chittuluru Adrienne Fouts Margarita Martinez-Moczygemba Margarita Martinez-Moczygemba Jonathan T. Lei David P. Huston David P. Huston Michael J. Tuvim Burton F. Dickey Scott E. Evans |
| author_facet | David L. Goldblatt David L. Goldblatt David L. Goldblatt Gabriella Valverde Ha Shradha Wali Vikram V. Kulkarni Michael K. Longmire Ana M. Jaramillo Rosha P. Chittuluru Adrienne Fouts Margarita Martinez-Moczygemba Margarita Martinez-Moczygemba Jonathan T. Lei David P. Huston David P. Huston Michael J. Tuvim Burton F. Dickey Scott E. Evans |
| author_sort | David L. Goldblatt |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T01:54:28Z |
| format | Article |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T01:54:28Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-dd1b05bdffe9477f901fdf3109e685012022-12-22T03:07:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.833380833380Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in miceDavid L. Goldblatt0David L. Goldblatt1David L. Goldblatt2Gabriella Valverde Ha3Shradha Wali4Vikram V. Kulkarni5Michael K. Longmire6Ana M. Jaramillo7Rosha P. Chittuluru8Adrienne Fouts9Margarita Martinez-Moczygemba10Margarita Martinez-Moczygemba11Jonathan T. Lei12David P. Huston13David P. Huston14Michael J. Tuvim15Burton F. Dickey16Scott E. Evans17Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesHoward Hughes Medical Institute, Chevy Chase, MD, United StatesUniversity of Texas Rio Grande Valley School of Medicine, Edinburg, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, Houston, TX, United StatesClinical Science and Translational Research Institute, Texas A&M Health Science Center, Houston, TX, United StatesClinical Science and Translational Research Institute, Texas A&M Health Science Center, Houston, TX, United StatesDepartment of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, Houston, TX, United StatesClinical Science and Translational Research Institute, Texas A&M Health Science Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United StatesAllergic 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.833380/fulltoll-like receptorsallergic asthmaallergen immunotherapyinnate immunitylung epithelial cellsallergen tolerance |
| spellingShingle | David L. Goldblatt David L. Goldblatt David L. Goldblatt Gabriella Valverde Ha Shradha Wali Vikram V. Kulkarni Michael K. Longmire Ana M. Jaramillo Rosha P. Chittuluru Adrienne Fouts Margarita Martinez-Moczygemba Margarita Martinez-Moczygemba Jonathan T. Lei David P. Huston David P. Huston Michael J. Tuvim Burton F. Dickey Scott E. Evans Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice Frontiers in Pharmacology toll-like receptors allergic asthma allergen immunotherapy innate immunity lung epithelial cells allergen tolerance |
| 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 | toll-like receptors allergic asthma allergen immunotherapy innate immunity lung epithelial cells allergen tolerance |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.833380/full |
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