CpG-ODN Signaling via Dendritic Cells-Expressing MyD88, but Not IL-10, Inhibits Allergic Sensitization

Author(s)

Alberca, Ricardo Wesley ^{[1, 2]} ; Gomes, Eliane ^[1] ; Russo, Momtchilo ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med FMUSP, Inst Trop Med, Dept Dermatol, Lab Dermatol & Immunodeficiencies L, BR-01246903 Sao Paulo - Brazil

• Document type: Journal article
• Source: VACCINES; v. 9, n. 7 JUL 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 13/24694-1 - Immunotherapy of experimental asthma by agonists of toll-like receptors, infection or tolerance
• Grantee: Momtchilo Russo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/02679-7 - Effect of maternal and paternal supplementation with antioxidant in pulmonary inflammatory process of the offspring of mice
• Grantee: Ricardo Wesley Alberca Custódio
• Support Opportunities: Scholarships in Brazil - Post-Doctoral