期刊
VACCINES
卷 9, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/vaccines9070743
关键词
allergic sensitization; eosinophils; dendritic cells; CpG-ODN; toll-like receptor; MyD88; IL-10
资金
- [2013/24694-1]
- [2019/02679-7]
This study explored the immunomodulatory effect of CpG-ODN on allergic sensitization to OVA with alum, focusing on dendritic cells expressing the MyD88 molecule and the suppressive IL-10 cytokine. CpG-ODN inhibited allergic sensitization and consequent lung allergic inflammation signaling through MyD88 pathway on dendritic cells. IL-10 was found to be dispensable for the inhibition of allergic lung Th2 responses by CpG-ODN.
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.
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