{"doi":"10.1101/2022.12.02.518944","title":"Type I Interferon Signaling on Antigen-Presenting Cells Blunts Cell-Mediated Immunity Toward <i>Listeria monocytogenes</i>","abstract":"Abstract Listeria monocytogenes is a facultative intracellular pathogen that has been used for decades to understand mechanisms of bacterial pathogenesis and both innate and adaptive immunity. L. monocytogenes is a potent activator of CD8 + T-cell mediated immunity. Yet how the innate immune response to infection modulates CD8 + T-cell responses is incompletely understood. Here, we utilize an attenuated L. monocytogenes vaccine platform to understand the impact of two innate immune pathways, type I interferon and inflammasomes, on CD8 + T-cell responses using a combination of mutant mice and genetically engineered L. monocytogenes . IFNAR −/− mice had the most robust T-cell response, while Caspase-1 −/− mice were not different from WT. We uncover a role for inflammasomes in the absence of type I interferon as Caspase-1 −/− /IFNAR −/− mice had fewer T-cells than IFNAR −/− . IFNAR −/− had more than twice as many memory precursors, promoting enhanced protection from rechallenge. Importantly, increased memory precursor T-cell abundance did not come at the expense of short-lived effectors. Vaccines genetically modified to induce lower type I interferon production yielded enhanced T-cell responses. Deficits from type I interferon signaling are dendritic cell-intrinsic, rather than acting on T-cells, as IFNAR −/− dendritic cells induced two-fold more T-cell proliferation than WT in ex vivo T-cell proliferation assays. Thus, modulating type I IFN signaling during vaccination may lead to more potent T-cell-based vaccines. Importantly, this suggests innate immune signaling significantly impacts the CD8 + T-cell response and suggests CD8 + T-cell quantity and quality are important factors to consider during rational vaccine design.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313574,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":467601,"name":"John‐Demian Sauer","orcid":"0000-0001-9367-794X","position":1,"is_corresponding":false},{"id":336007,"name":"Zachary Morrow","orcid":"0000-0001-6346-3270","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T00:33:44.454239Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}