In virto priming of the STING signaling pathway enhances the maturation and activation of dendritic cells induced by hepatitis B vaccine

This study investigates the role of the STING signaling pathway in enhancing dendritic cells (DCs) maturation and activation in response to the hepatitis B vaccine. By analyzing the GSE52894 dataset, we compared differentially expressed genes between mature dendritic cells (mDCs) and immature dendritic cells (iDCs). In vitro, iDCs were treated with the STING agonist 2 ' 3 '-cGAMP, either alone or in combination with lipopolysaccharide (LPS) or the hepatitis B vaccine, to assess the expression of costimulatory molecules and key signaling molecules in the STING pathway, including STING, pNF-kappa Bp65, and pIRF3. The results indicated that mDCs expressed significantly higher levels of STING mRNA compared to iDCs (P < 0.01). Treatment with 2 ' 3 '-cGAMP increased STING expression and activated downstream signaling molecules pNF-kappa Bp65 and pIRF3. Co-treatment with 2 ' 3 '-cGAMP and LPS upregulated costimulatory molecules (CD80, CD86, HLA-DR, CD11c) more effectively than LPS alone (P < 0.05). Co-treatment with 2 ' 3 '-cGAMP and the hepatitis B vaccine resulted in significantly higher expression of costimulatory molecules compared to vaccine-only treatment. Furthermore, co-treatment with 2 ' 3 '-cGAMP and the hepatitis B vaccine enhanced STING, pNF-kappa Bp65, and pIRF3 expression relative to vaccine alone. Mixed lymphocyte reaction assays demonstrated that the 2 ' 3 '-cGAMP and hepatitis B vaccine cotreatment group had a significantly stronger effect on the proliferation of CD4+T cells compared to the vaccineonly treatment group. In conclusion, 2 ' 3 '-cGAMP enhances DCs maturation and promotes CD4+T cells proliferation in response to the hepatitis B vaccine by activating the STING/IRF3 and STING/NF-kappa B pathways, highlighting its potential as an adjuvant to improve vaccine efficacy.