Alberca Ricardo Wesley, Gomes Eliane, Russo Momtchilo
Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, São Paulo 05508-000, Brazil.
Laboratory of Dermatology and Immunodeficiencies (LIM-56), Department of Dermatology, Institute of Tropical Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo 01246-903, Brazil.
Vaccines (Basel). 2021 Jul 5;9(7):743. doi: 10.3390/vaccines9070743.
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.
变应原特异性辅助性T细胞2（Th2）在变应原激发时协调过敏性嗜酸性粒细胞性肺部炎症的发展。使用明矾佐剂（一种2型佐剂）进行致敏已在过敏性肺病动物模型中广泛应用。相比之下，1型佐剂如CpG-ODN（一种合成的Toll样受体9激动剂）可抑制Th2免疫的发展。CpG-ODN诱导1型和抑制性细胞因子，影响Th2细胞分化。在此，我们研究了CpG-ODN对用明矾致敏卵清蛋白（OVA）的免疫调节作用，重点关注表达MyD88分子的树突状细胞（DCs）和抑制性白细胞介素-10（IL-10）细胞因子。利用特异性缺失MyD88分子的小鼠，我们发现CpG-ODN通过树突状细胞上的MyD88途径抑制过敏性致敏及随后的肺部过敏性炎症信号传导，但对B细胞无此作用。这种抑制与支气管肺泡灌洗液中IL-10产生增加有关。用IL-10缺陷型而非野生型小鼠的CpG-ODN致敏OVA，诱导炎症向Th1模式转变。使用用OVA脉冲的骨髓来源树突状细胞（BM-DCs）进行有或无CpG-ODN的致敏，我们发现IL-10对于CpG-ODN抑制过敏性肺部Th2反应并非必需。此外，DCs上缺乏IL-10不足以使CpG-ODN诱导免疫偏向Th1模式。因此，我们直接证实了DCs上MyD88途径在抑制过敏性致敏中的作用。
