| First Author | Alice AF | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 1 | Pages | 177-185 |
| PubMed ID | 29150567 | Mgi Jnum | J:253405 |
| Mgi Id | MGI:6108101 | Doi | 10.4049/jimmunol.1700909 |
| Citation | Alice AF, et al. (2018) Amplifying IFN-gamma Signaling in Dendritic Cells by CD11c-Specific Loss of SOCS1 Increases Innate Immunity to Infection while Decreasing Adaptive Immunity. J Immunol 200(1):177-185 |
| abstractText | Although prophylactic vaccines provide protective humoral immunity against infectious agents, vaccines that elicit potent CD8 T cell responses are valuable tools to shape and drive cellular immunity against cancer and intracellular infection. In particular, IFN-gamma-polarized cytotoxic CD8 T cell immunity is considered optimal for protective immunity against intracellular Ags. Suppressor of cytokine signaling (SOCS)1 is a cross-functional negative regulator of TLR and cytokine receptor signaling via degradation of the receptor-signaling complex. We hypothesized that loss of SOCS1 in dendritic cells (DCs) would improve T cell responses by accentuating IFN-gamma-directed immune responses. We tested this hypothesis using a recombinant Listeria monocytogenes vaccine platform that targets CD11c(+) DCs in mice in which SOCS1 is selectively deleted in all CD11c(+) cells. Unexpectedly, in mice lacking SOCS1 expression in CD11c(+) cells, we observed a decrease in CD8(+) T cell response to the L. monocytogenes vaccine. NK cell responses were also decreased in mice lacking SOCS1 expression in CD11c(+) cells but did not explain the defect in CD8(+) T cell immunity. We found that DCs lacking SOCS1 expression were functional in driving Ag-specific CD8(+) T cell expansion in vitro but that this process was defective following infection in vivo. Instead, monocyte-derived innate TNF-alpha and inducible NO synthase-producing DCs dominated the antibacterial response. Thus, loss of SOCS1 in CD11c(+) cells skewed the balance of immune response to infection by increasing innate responses while decreasing Ag-specific adaptive responses to infectious Ags. |
