School of Medicine Publications and Presentations
Document Type
Article
Publication Date
8-29-2022
Abstract
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.
Recommended Citation
Goldblatt DL, Valverde Ha G, Wali S, Kulkarni VV, Longmire MK, Jaramillo AM, Chittuluru RP, Fouts A, Martinez-Moczygemba M, Lei JT, Huston DP, Tuvim MJ, Dickey BF and Evans SE (2022) Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice. Front. Pharmacol. 13:833380. doi: 10.3389/fphar.2022.833380
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Frontiers in Pharmacology
DOI
10.3389/fphar.2022.833380
Academic Level
medical student
Comments
© 2022 Goldblatt, Valverde Ha, Wali, Kulkarni, Longmire, Jaramillo, Chittuluru, Fouts, Martinez-Moczygemba, Lei, Huston, Tuvim, Dickey and Evans.