STING is required in conventional dendritic cells for DNA vaccine induction of type I T helper cell-dependent antibody responses

Abstract

DNA vaccines elicit antibody, T helper cell, CD8+ T cell, and cytotoxic T lymphocyte (CTL) responses. Currently, little is known about the mechanism that DNA vaccines employ to induce adaptive immune responses. Studies have demonstrated that stimulator of interferon genes (STING) and conventional dendritic cells (cDCs) play critical roles in DNA vaccine-induced antibody and T cell responses. STING activation by double stranded DNA (dsDNA)-sensing proteins initiates the production of type I interferons (IFNs); however, the link between STING and cDCs remains unclear. In this study, I investigated the role of STING within cDCs on DNA vaccine induction of antibody and T cell responses. STING knockout (STING-/-) and conditional knockout mice that lacked STING in cDCs (cDC STING cKO) were immunized intramuscularly with a DNA vaccine that expressed influenza A nucleoprotein (pNP). Both STING-/- and cDC STING cKO mice had significantly lower type I T helper (Th1) antibody (anti-NP IgG2C) responses as well as lower frequencies of Th1-associated T cells (NP-specific IFN-γ+CD4+ T cells) post-immunization than wild-type (WT) and cDC STING littermate control mice. By contrast, all mice had similar Th2-type (NP-specific IgG1) antibody concentrations. Moreover, STING-/- mice developed significantly lower polyfunctional effector CD8+ T cells than WT, cDC STING cKO, and cDC STING littermate control mice. These findings suggest that STING within cDCs mediates DNA vaccine induction of Th1 responses, including IFN-γ+CD4+ T cell and Th1-type IgG2C antibody responses. The induction of CD8+ effector cell responses also requires STING, but not within cDCs. These findings provide new insight into the mechanism through which DNA vaccines induce Th1 responses.