During acute Trypanosoma cruzi infection highly susceptible mice deficient in natural killer cells are protected by a single α-galactosylceramide treatment

Summary The protective immune response against Trypanosoma cruzi is improved by treatment with the natural killer (NK) T-cell glycolipid antigen α-galactosylceramide (α-GalCer). A single α-GalCer treatment of mice before T. cruzi infection decreases parasitaemia and prolongs survival. This protection is dependent on CD1d-restricted NKT cells and interferon-γ (IFN-γ) suggesting that α-GalCer-activated NKT cells produce IFN-γ, which stimulates the cells of the innate and adaptive immune responses to provide protection. To learn which cells provide protection we investigate here α-GalCer treatment of mice deficient in different immune cells. Surprisingly, although NK cells provide protection against T. cruzi, and are a major source of IFN-γ following α-GalCer treatment, NK cells are not required for the α-GalCer-induced protection. The α-GalCer treatment of NK-cell-depleted mice controlled parasitaemia and prevented death. In contrast, phagocytes, helper T cells and cytotoxic T cells are required. Furthermore, α-GalCer treatment of MHC II–/– or CD8α–/– mice exacerbated the infection, demonstrating that α-GalCer treatment induces some responses that favour the parasite. In summary α-GalCer protection against T. cruzi required multiple cellular responses, but not the response of NK cells. These results provide useful information because α-GalCer is being developed as therapy for infections, autoimmune diseases, allergy and cancers.