IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii

• Published in: eLife 2021-04, Vol.10
• Main Authors: Clark, Joseph T, Christian, David A, Gullicksrud, Jodi A, Perry, Joseph A, Park, Jeongho, Jacquet, Maxime, Tarrant, James C, Radaelli, Enrico, Silver, Jonathan, Hunter, Christopher A
• Format: Article
• Language: English
• Subjects: Animals; Biopsy; Cytokines; Female; Humans; IL-1 family; IL-33; Immunity, Innate; Immunology and Inflammation; Infections; Inflammation; Innate immunity; innate lymphoid cells; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin 12; Interleukin-33 - genetics; Interleukin-33 - immunology; Lymphocytes; Lymphocytes - immunology; Lymphoid cells; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology and Infectious Disease; Monocytes; Parasite resistance; Parasites; Parasitic diseases; RAG1 protein; Replication; Toxoplasma - genetics; Toxoplasma - immunology; Toxoplasma gondii; Toxoplasmosis - genetics; Toxoplasmosis - immunology; Toxoplasmosis - parasitology; γ-Interferon
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.65614

IL-33 is an alarmin required for resistance to the parasite , but its role in innate resistance to this organism is unclear. Infection with promotes increased stromal cell expression of IL-33, and levels of parasite replication correlate with release of IL-33 in affected tissues. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R NK cells and ILC1s. In mice, where NK cells and ILC1 production of IFN-γ mediate innate resistance to , the loss of the IL-33R resulted in reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to mice resulted in a marked decrease in parasite burden, increased production of IFN-γ, and the recruitment and expansion of inflammatory monocytes associated with parasite control. These protective effects of exogenous IL-33 were dependent on endogenous IL-12p40 and the ability of IL-33 to enhance ILC production of IFN-γ. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance to .