1. The adjuvanticity of manganese for microbial vaccines via activating the IRF5 signaling pathway.
- Author
-
Cui C, Wang S, Lu W, Wang Y, Li J, Qu K, Yang M, Wang L, and Yu Y
- Subjects
- Animals, Bacterial Vaccines immunology, Chlorides administration & dosage, Female, Interferon Regulatory Factors immunology, Manganese Compounds administration & dosage, Mice, Mice, Inbred ICR, Signal Transduction drug effects, Bacterial Vaccines administration & dosage, Bacterial Vaccines metabolism, Interferon Regulatory Factors metabolism, Manganese administration & dosage, Signal Transduction physiology
- Abstract
Manganese (Mn
2+ ) has been reported to activate macrophages and NK cells, and to induce the production of type-I interferons (IFNs) by activating the cGAS-STING pathway. Few studies have been conducted on its adjuvanticity to microbial vaccines, and on the involvement of the interferon regulatory factor (IRF) 5 signaling pathway in the adjuvanticity. In this study, we demonstrated that Mn2+ could facilitate various microbial vaccines to induce enhanced antibody responses, and facilitate the influenza virus vaccine to induce protective immunity against the influenza virus challenge. When formulated in vaccines, Mn2+ could activate murine CD4+ T cells, CD8+ T cells, B cells and DCs, and induce the expression and phosphorylation of TANK-binding kinase 1 (TBK1) and IRF5 in the splenocytes of the immunized mice, resulting in the increased expression of type-I IFNs, TNF-α, B cell-activating factor of the TNF family (BAFF) and B lymphocyte-induced maturation protein-1 (Blimp-1). The induced TBK1 could recruit and bind the IRF5. Furthermore, the Mn2+ induced expression of IRF5 and Blimp-1 was prohibited by a IRF5 interfering oligonucleotide. The data suggest the Mn2+ could be used as a novel type of adjuvants for microbial vaccines, and the activation of IRF5 signaling pathway might involve in the adjuvanticity., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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