Abstract
Changing the immune responses to allergens is the cornerstone of allergen immunotherapy. Allergen-specific immunotherapy that consists of repeated administration of increasing doses of allergen extract is potentially curative. The major inconveniences of allergen-specific immunotherapy include failure to modify immune responses, long-term treatment leading to non-compliance and the potential for developing life-threating anaphylaxis. Here we investigated the effect of a novel liposomal formulation carrying low dose of allergen combined with CpG-ODN, a synthetic TLR9 agonist, on established allergic lung inflammation. We found that challenge with allergen (OVA) encapsulated in cationic liposome induced significantly less severe cutaneous anaphylactic reaction. Notably, short-term treatment (three doses) with a liposomal formulation containing co-encapsulated allergen plus CpG-ODN, but not allergen or CpG-ODN alone, reversed an established allergic lung inflammation and provided long-term protection. This liposomal formulation was also effective against allergens derived from Blomia tropicalis mite extract. The attenuation of allergic inflammation was not associated with increased numbers of Foxp3-positive or IL-10-producing regulatory T cells or with increased levels of IFN-gamma in the lungs. Instead, the anti-allergic effect of the liposomal formulation was dependent of the innate immune signal transduction generated in CD11c-positive putative dendritic cells expressing MyD88 molecule. Therefore, we highlight the pivotal role of dendritic cells in mediating the attenuation of established allergic lung inflammation following immunotherapy with a liposomal formulation containing allergen plus CpG-ODN.
Highlights
Asthma is a complex chronic respiratory disorder characterized by episodes of cough and wheezing with increased mucus secretion that results in variable airflow limitation and airway hyper-responsiveness [1]
We found that while the total number of cells and eosinophils were increased in Bronchoalveolar Lavage (BAL) of allergic mice after OVA challenges compared to Control group, the treatment with liposomal formulation containing allergen and CpG significantly reduced the total cell and eosinophil counts in BAL when compared to Allergic group (Figures 3B,C)
Using MyD88-deficient mice (MyD88KO) and C57BL/6 wild-type (WT) mice we found that treatment with liposomal formulation reduced the number of total cells, eosinophils, and the levels of IL-5 in the BAL in WT but not in MyD88KO mice when compared with the respective Allergic groups (Figures 5A–C)
Summary
Asthma is a complex chronic respiratory disorder characterized by episodes of cough and wheezing with increased mucus secretion that results in variable airflow limitation and airway hyper-responsiveness [1]. Patients with a high Th2 endotype show elevated levels of IL-4, IL-5, IL-9, and IL-13 in the airways [4, 5] These cytokines mediate allergic eosinophilic inflammation and isotype switching to IgE [6]. It is postulated that asthma can be either prevented or suppressed by intrinsic and/or extrinsic factors that collectively modify the immune responses to airborne allergens [7]. The cellular and molecular mechanisms of the immunological switch against airborne allergens are still elusive. Different mechanisms such as maturation of the immune system, immune-deviation toward a Th1 profile, active suppression by different regulatory cells including Foxp3-expressing regulatory T (Treg) cells, IL10-producing T or B regulatory cells, or anergy have been proposed [9]. We have previously shown that among TLR agonists studied, the TLR9 agonist CpG-oligodeoxynucleotides, hereafter denominated CpG, was the most effective in preventing allergic sensitization [21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
