Diet-induced dyslipidemia leads to enhanced IFN-g production by mycolic acid-specific T cells

Diet-induced dyslipidemia, characterized by elevated plasma LDL-cholesterol levels, has been shown to affect host defense against infections, including Mycobacterium tuberculosis (Mtb). Although the impact of diet-induced dyslipidemia on conventional T cell functions is well studied, its influence on group 1-restricted T cells during Mtb infection is very limited. In this study, we generated a unique double-transgenic mouse model expressing human CD1 and mycolic acid (MA)-specific CD1b-restricted T cell receptor in a Rag-deficient and low-density lipoprotein receptor-deficient background to investigate how diet-induced dyslipidemia impacts functionality of MA-specific T cells and its effect on anti-Mtb immunity. While dyslipidemia augmented IFN-g production by MA-specific T cells, it paradoxically led to increased apoptosis and thus compromised their ability to restrict Mtb growth in vivo. These findings may elucidate the complex interplay between diet-induced dyslipidemia and lipid antigen-specific T-cell responses in the context of Mtb infection, offering insights that could inform potential therapeutic approaches addressing dyslipidemia-induced changes in T-cell functions.