Characterizing the mechanisms underpinning interleukin-15Rα-mediated protection against sepsis and candidiasis.

The interleukin (IL)-15Rα receptor has crucial, protective roles in sepsis and candidiasis via binding to its ligand, IL-15. However, the underlying mechanisms remain largely unexplored. In our study, we first confirmed the protective effects of IL-15 using clinical samples from patients with sepsis and candidiasis, and also in animal models with those conditions. We therapeutically administered IL-15 to IL-15Rα-deficient mice to elucidate the roles of IL-15Rα in sepsis and candidiasis treatment. Bacterial and fungal infections expedite mortality, caused organ damage, elevated the microbial burden in organs, and impaired macrophage recruitment, and subsequent microbial killing capacity. Notably, these adverse effects were alleviated via recombinant IL-15 supplementation, but this did not improve compromised conditions in IL-15Rα-deficient mice with sepsis. We show that IL-15Rα is required for protection against both bacterial and fungal sepsis, suggesting that this receptor could become a potential target for treating clinical sepsis and may hold significant clinical therapeutic value.