@misc{10481/97126,
year = {2023},
month = {6},
url = {https://hdl.handle.net/10481/97126},
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.},
organization = {National Institutes of Health grants
R01AI167421 and R01AI112619 to J.M.C and L.R
and R01AI133976, R01AI145890, R01AI152268 to
L.R},
organization = {FEDER/Junta de
Andalucía-Consejería de Transformación
Económica, Industria, Conocimiento y
Universidades (B-FQM-130-UGR20 and P20_00028)},
organization = {The NIH training grants T32
AI007509 supported A.B and T32 AI055396
supported A. F},
publisher = {PLOS ONE},
title = {CD1 and iNKT cells mediate immune responses against the GBS hemolytic lipid toxin induced by a non-toxic analog},
doi = {10.1371/journal.ppat.1011490},
author = {Furuta, Anna and Coleman, Michelle and Casares López, Raquel and Seepersaud, Ravin and Orvis, Austyn and Brokaw, Alyssa and Quach, Phoenicia and Nguyen, Shayla and Sweeney, Erin and Sharma, Kavita and Wallen, Grace and Sanghavi, Rhea and Mateos-Gil, Jaime and Cuerva Carvajal, Juan Manuel and Millán Delgado, Alba and Rajagopal, Lakshmi},
}