STING-dependent type-1 interferon restrains schistosome immunopathology via down-regulation of the CD209a lectin receptor
| Autor: | Parisa Kalantari, Ilana Shecter, Andrea Pilotta Gois, Jacob Hopkins, Yoelkys Morales, Shruti Sharma, Miguel Stadecker |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:227.11-227.11 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.204.supp.227.11 |
| Popis: | Infection with the helminth parasite Schistosoma mansoni causes morbidity and mortality via a pathogenic host CD4 T cell-mediated immune response directed against parasite egg antigens. We now demonstrate that stimulation of dendritic cells (DCs) with schistosome eggs induces robust IFNβ production in a manner dependent on the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon genes (STING) cytosolic DNA sensing pathway, resulting in the suppression of proinflammatory IL-1β and IL-23 production and in Th17 cell activation. Consistent with these results, low-pathology BL/6 mice lacking STING exhibited markedly enhanced hepatic granulomatous inflammation associated with significantly increased Th17 and diminished Th2 cytokine responses. Mechanistically, IFNβ acts by suppressing DC expression and function of CD209a, a C-type lectin receptor associated with severe schistosome immunopathology. Importantly, there was an increased baseline CD209a expression in unstimulated DCs from STING−/− mice, suggesting a role for constitutive IFN signaling. Our findings demonstrate that innate, cGAS/STING-dependent sensing of parasite DNA represents a novel pathway inducing type I IFN production, which protects the host from excessive inflammation and immunopathology in schistosomiasis. This work is supported by NIAID grant R01 AI018919 to MJS. |
| Databáze: | OpenAIRE |
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