| First Author | Kalantari P | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 13 | Pages | e2211047120 |
| PubMed ID | 36943884 | Mgi Jnum | J:340769 |
| Mgi Id | MGI:7530602 | Doi | 10.1073/pnas.2211047120 |
| Citation | Kalantari P, et al. (2023) The balance between gasdermin D and STING signaling shapes the severity of schistosome immunopathology. Proc Natl Acad Sci U S A 120(13):e2211047120 |
| abstractText | There is significant disease heterogeneity among mouse strains infected with the helminth Schistosoma mansoni. Here, we uncover a unique balance in two critical innate pathways governing the severity of disease. In the low-pathology setting, parasite egg-stimulated dendritic cells (DCs) induce robust interferon (IFN)beta production, which is dependent on the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) cytosolic DNA sensing pathway and results in a Th2 response with suppression of proinflammatory cytokine production and Th17 cell activation. IFNbeta induces signal transducer and activator of transcription (STAT)1, which suppresses CD209a, a C-type lectin receptor associated with severe disease. In contrast, in the high-pathology setting, enhanced DC expression of the pore-forming protein gasdermin D (Gsdmd) results in reduced expression of cGAS/STING, impaired IFNbeta, and enhanced pyroptosis. Our findings demonstrate that cGAS/STING signaling represents a unique mechanism inducing protective type I IFN, which is counteracted by Gsdmd. |
