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CD1 and iNKT cells mediate immune responses against the GBS hemolytic lipid toxin induced by a non-toxic analog
| dc.contributor.author | Furuta, Anna | |
| dc.contributor.author | Coleman, Michelle | |
| dc.contributor.author | Casares López, Raquel | |
| dc.contributor.author | Seepersaud, Ravin | |
| dc.contributor.author | Orvis, Austyn | |
| dc.contributor.author | Brokaw, Alyssa | |
| dc.contributor.author | Quach, Phoenicia | |
| dc.contributor.author | Nguyen, Shayla | |
| dc.contributor.author | Sweeney, Erin | |
| dc.contributor.author | Sharma, Kavita | |
| dc.contributor.author | Wallen, Grace | |
| dc.contributor.author | Sanghavi, Rhea | |
| dc.contributor.author | Mateos-Gil, Jaime | |
| dc.contributor.author | Cuerva Carvajal, Juan Manuel | |
| dc.contributor.author | Millán Delgado, Alba | |
| dc.contributor.author | Rajagopal, Lakshmi | |
| dc.date.accessioned | 2024-11-20T08:42:18Z | |
| dc.date.available | 2024-11-20T08:42:18Z | |
| dc.date.issued | 2023-06-29 | |
| dc.identifier.citation | Furuta, A. et. al. PLoS Pathog 19(6): e1011490. [https://doi.org/10.1371/journal.ppat.1011490] | es_ES |
| dc.identifier.uri | https://hdl.handle.net/10481/97126 | |
| dc.description.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. | es_ES |
| dc.description.sponsorship | National Institutes of Health grants R01AI167421 and R01AI112619 to J.M.C and L.R and R01AI133976, R01AI145890, R01AI152268 to L.R | es_ES |
| dc.description.sponsorship | FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (B-FQM-130-UGR20 and P20_00028) | es_ES |
| dc.description.sponsorship | The NIH training grants T32 AI007509 supported A.B and T32 AI055396 supported A. F | es_ES |
| dc.language.iso | eng | es_ES |
| dc.publisher | PLOS ONE | es_ES |
| dc.rights | Atribución 4.0 Internacional | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
| dc.title | CD1 and iNKT cells mediate immune responses against the GBS hemolytic lipid toxin induced by a non-toxic analog | es_ES |
| dc.type | journal article | es_ES |
| dc.rights.accessRights | open access | es_ES |
| dc.identifier.doi | 10.1371/journal.ppat.1011490 | |
| dc.type.hasVersion | VoR | es_ES |
