{"doi":"10.1101/2022.11.02.514909","title":"Human FcγRIIIa activation on splenic macrophages drives the in vivo pathogenesis of dengue disease","abstract":"Abstract Although dengue virus (DENV) infection typically causes asymptomatic disease, DENV-infected patients can experience severe complications. A risk factor for symptomatic disease is pre-existing anti-DENV IgG antibodies. Cellular assays suggested that these antibodies can enhance viral infection of Fcγ receptor (FcγR)-expressing myeloid cells. Recent studies, however, revealed more complex interactions between anti-DENV antibodies and specific FcγRs by demonstrating that modulation of the IgG Fc glycan correlates with disease severity. To investigate the in vivo mechanisms of antibody-mediated dengue pathogenesis, we developed a mouse model for dengue disease that recapitulates the unique complexity of human FcγRs. Our studies reveal that the in vivo pathogenic activity of anti-DENV IgG antibodies is exclusively mediated through engagement of FcγRIIIa expressed on splenic macrophages, resulting in inflammatory sequelae and mortality. These findings highlight the importance of IgG-FcγRIIIa interactions in dengue disease, with important implications in the design of safer vaccination approaches and effective therapeutic strategies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299589,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"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":237515,"name":"Kevin S. Kao","orcid":"0000-0003-1918-2097","position":1,"is_corresponding":false},{"id":228346,"name":"Margaret R. MacDonald","orcid":"0000-0001-5177-2068","position":2,"is_corresponding":false},{"id":628655,"name":"Tineke Cantaert","orcid":"0000-0002-8911-1502","position":3,"is_corresponding":false},{"id":104737,"name":"Charles M. Rice","orcid":"0000-0003-3087-8079","position":4,"is_corresponding":false},{"id":109914,"name":"Jeffrey V. Ravetch","orcid":"0000-0003-2024-9041","position":5,"is_corresponding":false},{"id":109912,"name":"Stylianos Bournazos","orcid":"0000-0001-5466-5620","position":6,"is_corresponding":false},{"id":237514,"name":"Rachel Yamin","orcid":"0000-0002-3603-526X","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T00:31:44.904250Z","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":[]}