The adjuvanticity of manganese for microbial vaccines via activating the IRF5 signaling pathway

Area of Science:

• Immunology
• Vaccinology
• Molecular Biology

Background:

• Manganese (Mn²⁺) activates immune cells like macrophages and NK cells, and induces type-I interferons (IFNs) via the cGAS-STING pathway.
• Limited research exists on Mn²⁺'s role as an adjuvant in microbial vaccines and its connection to the interferon regulatory factor (IRF) 5 signaling pathway.

Purpose of the Study:

• To investigate the adjuvanticity of Mn²⁺ in microbial vaccines.
• To explore the involvement of the IRF5 signaling pathway in Mn²⁺-mediated adjuvanticity.

Main Methods:

• Mice were immunized with various microbial vaccines formulated with Mn²⁺.
• Immune cell activation, cytokine production, and key signaling molecule expression (TBK1, IRF5) were analyzed in splenocytes.
• The effect of an IRF5 interfering oligonucleotide on Mn²⁺-induced responses was assessed.

Main Results:

• Mn²⁺ enhanced antibody responses for various microbial vaccines and provided protection against influenza virus challenge when used with the influenza vaccine.
• Mn²⁺ activated murine CD4⁺ T cells, CD8⁺ T cells, B cells, and DCs.
• Mn²⁺ induced the expression and phosphorylation of TBK1 and IRF5, leading to increased type-I IFNs, TNF-α, BAFF, and Blimp-1. TBK1 recruited and bound IRF5.
• IRF5 and Blimp-1 expression induced by Mn²⁺ was blocked by an IRF5 interfering oligonucleotide.

Conclusions:

• Mn²⁺ shows potential as a novel adjuvant for microbial vaccines, enhancing both antibody and cellular immune responses.
• The activation of the IRF5 signaling pathway appears to be involved in the adjuvanticity of Mn²⁺.