{"doi":"10.1371/journal.ppat.1011490","title":"CD1 and iNKT cells mediate immune responses against the GBS hemolytic lipid toxin induced by a non-toxic analog","abstract":"Although hemolytic lipids have been discovered from many human pathogens including Group B Streptococcus (GBS), strategies that neutralize their function are lacking. GBS is a leading cause of pregnancy-associated neonatal infections, and adult GBS infections are on the rise. The GBS hemolytic lipid toxin or granadaene, is cytotoxic to many immune cells including T and B cells. We previously showed that mice immunized with a synthetic nontoxic analog of granadaene known as R-P4 had reduced bacterial dissemination during systemic infection. However, mechanisms important for R-P4 mediated immune protection was not understood. Here, we show that immune serum from R-P4-immunized mice facilitate GBS opsonophagocytic killing and protect naïve mice from GBS infection. Further, CD4+ T cells isolated from R-P4-immunized mice proliferated in response to R-P4 stimulation in a CD1d- and iNKT cell-dependent manner. Consistent with these observations, R-P4 immunized mice lacking CD1d or CD1d-restricted iNKT cells exhibit elevated bacterial burden. Additionally, adoptive transfer of iNKT cells from R-P4 vaccinated mice significantly reduced GBS dissemination compared to adjuvant controls. Finally, maternal R-P4 vaccination provided protection against ascending GBS infection during pregnancy. These findings are relevant in the development of therapeutic strategies targeting lipid cytotoxins.","journal":"PLoS Pathogens","year":2023,"id":365747,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336523,"name":"Michelle M. Coleman","orcid":"0000-0002-6752-3266","position":1,"is_corresponding":false},{"id":482886,"name":"Raquel Casares","orcid":"0000-0002-3148-8112","position":2,"is_corresponding":false},{"id":453894,"name":"Ravin Seepersaud","orcid":null,"position":3,"is_corresponding":false},{"id":338203,"name":"Austyn Orvis","orcid":null,"position":4,"is_corresponding":false},{"id":476752,"name":"Alyssa Brokaw","orcid":"0000-0002-2399-4912","position":5,"is_corresponding":false},{"id":476751,"name":"Phoenicia Quach","orcid":"0000-0002-2402-4993","position":6,"is_corresponding":false},{"id":682664,"name":"Shayla Nguyen","orcid":null,"position":7,"is_corresponding":false},{"id":938601,"name":"Erin Sweeney","orcid":null,"position":8,"is_corresponding":false},{"id":681698,"name":"Kavita Sharma","orcid":"0000-0002-5515-9153","position":9,"is_corresponding":false},{"id":1122011,"name":"Grace Wallen","orcid":null,"position":10,"is_corresponding":false},{"id":1078212,"name":"Rhea Sanghavi","orcid":null,"position":11,"is_corresponding":false},{"id":1121606,"name":"Jaime Mateos","orcid":"0000-0002-5819-9927","position":12,"is_corresponding":false},{"id":482890,"name":"Juan M. Cuerva","orcid":"0000-0001-6896-9617","position":13,"is_corresponding":false},{"id":482887,"name":"Alba Millán","orcid":"0000-0003-2754-270X","position":14,"is_corresponding":false},{"id":336527,"name":"Lakshmi Rajagopal","orcid":"0000-0003-3373-2323","position":15,"is_corresponding":false},{"id":290170,"name":"Anna Furuta","orcid":null,"position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T01:14:50.885797Z","pmid":"37384812","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":[]}