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-γ–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-γ–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-α 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.
This work was supported by Congressionally Directed Medical Research Programs Grant W81XWH-11-PRCRP-DA (to K.S.B.) and National Institutes of Health Grants R01CA182311 (to M.J.G.) and R21AI126151 (to M.R.C.).
The online version of this article contains supplemental material.
Abbreviations used in this article:
- ΔactA ActA-QV
- brain–heart infusion
- bone marrow–derived DC
- dendritic cell
- intracellular cytokine staining
- inducible NO synthase
- MHC class II
- quantitative real-time PCR
- suppressor of cytokine signaling
- stimulator of IFN genes
- TNF-α and inducible NO synthase–producing DC
- Received June 22, 2017.
- Accepted October 23, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.