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

• Published in: PLoS pathogens Vol. 17; no. 1; p. e1008299
• Main Authors: López-Yglesias, Américo H, Burger, Elise, Camanzo, Ellie, Martin, Andrew T, Araujo, Alessandra M, Kwok, Samantha F, Yarovinsky, Felix
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2021; Public Library of Science (PLoS)
• Subjects: Amino acid sequence; Animals; Biology and Life Sciences; CD4 antigen; CD8 antigen; Conserved sequence; Critical components; Crosstalk; Cysts; Cytokines; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - microbiology; Experiments; Female; Helper cells; Immune response; Immune system; Immunity, Innate - immunology; Infections; Inflammation; Interferon; Interferon consensus sequence-binding protein; Interferon Regulatory Factors - physiology; Interferon-gamma - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Killer Cells, Natural - microbiology; Lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes - microbiology; Lymphocytes T; Male; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid cells; Natural killer cells; Parasites; Pathogens; Protozoa; Research and Analysis Methods; Rodents; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Toxoplasma - immunology; Toxoplasma - metabolism; Toxoplasmosis - immunology; Toxoplasmosis - metabolism; Toxoplasmosis - microbiology; Transcription factors; γ-Interferon
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008299

Host 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.