T-bet-dependent ILC1- and NK cell-derived IFN-? mediates cDC1-dependent host resistance against Toxoplasma gondii.

ABSTRACT: Host resistance against intracellular pathogens requires a rapid IFN-? mediated immune response. We reveal that T-bet-dependent production of IFN-? 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-? identified that ILC1s and to a lesser degree NK, but not TH1 cells, were involved in the regulation of inflammatory DCs via IFN-?. Mechanistically, we established that T-bet dependent innate IFN-? 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-? by ILC1 and NK cells is indispensable for host resistance against intracellular infection via maintaining IRF8+ inflammatory DCs at the site of infection.

SUBMITTER: Lopez-Yglesias AH 

PROVIDER: S-EPMC7875365 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature