López-Yglesias, Américo H.Burger, EliseCamanzo, EllieMartin, Andrew T.Araujo, Alessandra M.Kwok, Samantha F.Yarovinsky, Felix2025-03-312025-03-312021-01-19López-Yglesias AH, Burger E, Camanzo E, et al. T-bet-dependent ILC1- and NK cell-derived IFN-γ mediates cDC1-dependent host resistance against Toxoplasma gondii. PLoS Pathog. 2021;17(1):e1008299. Published 2021 Jan 19. doi:10.1371/journal.ppat.1008299https://hdl.handle.net/1805/46690Host resistance against intracellular pathogens requires a rapid IFN-γ mediated immune response. We reveal that T-bet-dependent production of IFN-γ is essential for the maintenance of inflammatory DCs at the site of infection with a common protozoan parasite, Toxoplasma gondii. A detailed analysis of the cellular sources for T-bet-dependent IFN-γ identified that ILC1s and to a lesser degree NK, but not TH1 cells, were involved in the regulation of inflammatory DCs via IFN-γ. Mechanistically, we established that T-bet dependent innate IFN-γ is critical for the induction of IRF8, an essential transcription factor for cDC1s. Failure to upregulate IRF8 in DCs resulted in acute susceptibility to T. gondii infection. Our data identifies that T-bet dependent production of IFN-γ by ILC1 and NK cells is indispensable for host resistance against intracellular infection via maintaining IRF8+ inflammatory DCs at the site of infection.en-USAttribution 4.0 InternationalDendritic cellsToxoplasmosisLymphocytesArticle