TRIM32 positively regulates c-di-GMP-Induced type I interferon signaling pathway in Listeria monocytogenes infection.

Abstract

Listeria monocytogenes (Lm) poses a significant threat to human health. TRIM32, an E3 ubiquitin ligase, plays a critical role in regulating immune responses to pathogen infections. Previous studies have shown that TRIM32 deficiency significantly impairs IFN-β production. In this study, we demonstrate that TRIM32 enhances IFN-β release upon activation by cyclic di-GMP (c-di-GMP). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that TRIM32 deficiency upregulates genes associated with metabolic pathways while downregulating those involved in cytokine signaling and inflammatory responses. Western blot analysis further indicated a significant reduction in ERK and JNK phosphorylation in splenocytes and peritoneal macrophages, suggesting that TRIM32 modulates the MAPK signaling pathway. Additionally, the duration of p38, STAT, and TBK1 phosphorylation was shortened in bone marrow-derived macrophages. Collectively, these findings highlight the role of TRIM32 in enhancing the host immune response against Lm infection.