2023 | Parisa Kalantari

Parisa Kalantari, Assistant Professor of Immunology 

Awarded Publication

"The balance between gasdermin D and STING signaling shapes the severity of schistosome immunopathology", Proceedings of the National Academy of Sciences 120, No. 13 (2023)

Parisa Kalantari, Ilana Shecter, Jacob Hopkins, Andrea Pilotta Gois, Yoelkys Morales, Bijan F. Harandi, Shruti Sharma, and Miguel J. Stadecker

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)β 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. IFNβ 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 IFNβ, and enhanced pyroptosis. Our findings demonstrate that cGAS/STING signaling represents a unique mechanism inducing protective type I IFN, which is counteracted by Gsdmd.