Exacerbated Salmonellosis in poly(ADP-ribose) polymerase 14 deficient mice

Salmonella enterica serovar Typhimurium infection triggers a robust immune response in the host, but the molecular mechanisms regulating this response are not fully understood. Parp14 has been shown to enhance type I interferon responses and influence bacterial resistance, particularly in macrophages. To explore the role of Parp14 in immune regulation, we investigated Salmonella infection in Parp14 knockout mice over 5 days. On day 1 post-infection (p.i.), Parp14-deficient mice displayed elevated bacterial loads in the liver, but no differences in other tissues. By day 5, bacterial counts in the proximal colon were slightly lower in Parp14 knockout mice compared to wild-type controls, suggesting Parp14 regulates immune responses across multiple cell types, including epithelial cells. Histopathological analyses revealed increased immune cell infiltration, goblet cell loss, and tissue erosion in the proximal colon of Parp14-deficient mice on day 5 p.i. RNA-seq data from proximal colon tissue identified impaired expression of immune response genes, including Ccl2, Il1b, and Il6, which are critical for early-stage infection defense. Further analysis revealed downregulation of genes involved in cellular adhesion and cytoskeleton maintenance. These findings indicate that Parp14 is essential for an effective early innate immune response and for maintaining epithelial integrity during Salmonella infection, highlighting its potential as a therapeutic target for bacterial infections. Overall design: To investigate the transcriptome changes in colon of Parp14-deficient mice when compared to wt mice in resting state and post Salmonella infection, we performed bulk tissue RNA-Seq analysis of the mouse colon proximal sections 1-day post-infection.