Journal Article

T cell intrinsic STAT1 signaling prevents aberrant Th1 responses during acute toxoplasmosis

Doyle, Laura P., Nivelo, Luis, Hennighausen, Lothar, Jankovic, Dragana, Schultz, Aaron B., O’Shea, John J., Villarino, Alejandro V., Vitari, Nicolas, Kugler, David G., Ristin, Svetlana

2023

Overview

Infection-induced T cell responses must be properly tempered and terminated to prevent immuno-pathology. Using transgenic mice, we demonstrate that T cell intrinsic STAT1 signaling is required to curb inflammation during acute infection with Toxoplasma gondii . Specifically, we report that mice lacking STAT1 selectively in T cells expel parasites but ultimately succumb to lethal immuno-pathology characterized by aberrant Th1-type responses with reduced IL-10 and increased IL-13 production. We also find that, unlike STAT1, STAT3 is not required for induction of IL-10 or suppression of IL-13 during acute toxoplasmosis. Each of these findings was confirmed in vitro and ChIP-seq data mining showed that STAT1 and STAT3 co-localize at the Il10 locus, as well as loci encoding other transcription factors that regulate IL-10 production, most notably Maf and Irf4 . These data advance basic understanding of how infection-induced T cell responses are managed to prevent immuno-pathology and provide specific insights on the anti-inflammatory properties of STAT1, highlighting its role in shaping the character of Th1-type responses.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Anti-inflammatory agents / Antigens / cytokine / Cytokines / Flow cytometry / Gene loci / IL-10 (interleukin 10) / IL-27 (interleukin 27) / Immunology / Infections / Interferon regulatory factor 4 / Interleukin 10 / Interleukin 13 / JAK - STAT signaling pathway / Lymphocytes / Lymphocytes T / Parasites / Pathology / Protozoa / Spleen / STAT1 / Stat1 protein / STAT3 / Stat3 protein / T cell receptors / Toxoplasmosis / Transcription factors / Transgenic mice