Dynamics and function of group 1 CD1-restricted T cells during disseminated Staphylococcus aureus infection

Abstract

Abstract Staphylococcus aureus (SA) is frequently associated with nosocomial and community-acquired infections. Some promising vaccine candidates act by priming conventional T cell responses, but less is known about the contribution of non-conventional T cells to SA infection. Group 1 CD1-restricted T cells are a unique subset of T cells that respond to lipid antigens presented by group 1 CD1 (CD1a, -b, –c) molecules. These molecules have low polymorphism in their antigen-binding grooves, making them attractive vaccine targets. Previous studies have shown that group 1 CD1-restricted T cells respond to Mycobacterium tuberculosis (Mtb) lipids. As group 1 CD1 molecules can accommodate a variety of lipid species, we questioned whether and how group 1 CD1-restricted T cells can be activated by SA lipids. Using a transgenic mouse strain expressing human group 1 CD1 molecules (hCD1Tg), we found that group 1 CD1-restricted T cells recognize SA lipid during primary infection. hCD1Tg mice were also protected against SA kidney pathology compared with WT control mice at late times post-infection. Group 1 CD1-restricted T cells produced both IL-17 and IFN-γ in response to SA lipid. Fractionation of SA lipid into 11 discrete parts found that portions enriched in cardiolipins and phosphatidyl glycerol contained immunodominant group 1 CD1-restricted antigens. Finally, group 1 CD1-restricted SA lipid-specific T cells can be specifically detected via FACS to ultimately assay differences in gene expression between these and conventional SA Ag-specific T cells. These findings suggest a role for CD1-restricted, SA lipid-specific T cells in control of systemic SA infection, with strong implications for vaccine design.