CD1 and iNKT cells mediate immune responses against the GBS hemolytic lipid toxin induced by a non-toxic analog Furuta, Anna Coleman, Michelle Casares López, Raquel Seepersaud, Ravin Orvis, Austyn Brokaw, Alyssa Quach, Phoenicia Nguyen, Shayla Sweeney, Erin Sharma, Kavita Wallen, Grace Sanghavi, Rhea Mateos-Gil, Jaime Cuerva Carvajal, Juan Manuel Millán Delgado, Alba Rajagopal, Lakshmi 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. 2024-11-20T08:42:18Z 2024-11-20T08:42:18Z 2023-06-29 journal article Furuta, A. et. al. PLoS Pathog 19(6): e1011490. [https://doi.org/10.1371/journal.ppat.1011490] https://hdl.handle.net/10481/97126 10.1371/journal.ppat.1011490 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional PLOS ONE