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CpG-ODN Signaling via Dendritic Cells-Expressing MyD88, but Not IL-10, Inhibits Allergic Sensitization
| Content Provider | MDPI |
|---|---|
| Author | Alberca, Ricardo Gomes, Eliane Russo, Momtchilo |
| Copyright Year | 2021 |
| Description | Allergen-specific T helper (Th)2 cells orchestrate upon allergen challenge the development of allergic eosinophilic lung inflammation. Sensitization with alum adjuvant, a type 2 adjuvant, has been used extensively in animal models of allergic lung disease. In contrast, type 1 adjuvants like CpG-ODN, a synthetic toll-like receptor 9 agonist, inhibit the development of Th2 immunity. CpG-ODN induce type 1 and suppressive cytokines that influence Th2 cell differentiation. Here, we investigated the immune modulatory effect of CpG-ODN on allergic sensitization to OVA with alum focusing on dendritic cells (DCs) expressing the MyD88 molecule and the suppressive IL-10 cytokine. Using mice with specific cell deletion of MyD88 molecule, we showed that CpG-ODN suppressed allergic sensitization and consequent lung allergic inflammation signaling through the MyD88 pathway on dendritic cells, but not on B-cells. This inhibition was associated with an increased production of IL-10 in the bronchoalveolar lavage fluid. Sensitization to OVA with CpG-ODN of IL-10-deficient, but not wild-type mice, induced a shift towards Th1 pattern of inflammation. Employing bone marrow-derived dendritic cells (BM-DCs) pulsed with OVA for sensitizations with or without CpG-ODN, we showed that IL-10 is dispensable for the inhibition of allergic lung Th2 responses by CpG-ODN. Moreover, the lack of IL-10 on DCs was not sufficient for the CpG-ODN-induced immune-deviation towards a Th1 pattern. Accordingly, we confirmed directly the role of MyD88 pathway on DCs in the inhibition of allergic sensitization. |
| Starting Page | 743 |
| e-ISSN | 2076393X |
| DOI | 10.3390/vaccines9070743 |
| Journal | Vaccines |
| Issue Number | 7 |
| Volume Number | 9 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-07-05 |
| Access Restriction | Open |
| Subject Keyword | Vaccines Immunology Allergic Sensitization Eosinophils Dendritic Cells Cpg-odn Toll-like Receptor Myd88 Il-10 |
| Content Type | Text |
| Resource Type | Article |