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

Area of Science:

• Immunology
• Microbiology
• Molecular Biology

Background:

• Salmonella Typhimurium infection causes significant mucosal inflammation with incompletely understood molecular mechanisms.
• Poly(ADP-ribose) polymerase (PARP) family proteins, including Parp14, are implicated in inflammatory responses, but their physiological roles remain largely unclear.

Purpose of the Study:

• To investigate the function of the nucleocytoplasmic protein Parp14 in a mouse model of Salmonella Typhimurium infection.
• To elucidate the role of Parp14 in mucosal inflammation and host defense against S. Typhimurium.

Main Methods:

• Systemic Parp14 knockout mouse model.
• Histopathological analysis of infected tissues.
• Bulk tissue and single-cell RNA sequencing (RNA-Seq).
• TaqMan quantitative PCR (qPCR) assays.
• Immunohistochemistry.

Main Results:

• Parp14-deficient mice exhibited exacerbated intestinal histopathology, including increased immune cell infiltration, goblet cell loss, and epithelial erosion.
• A defective Th17 immune response was observed in Parp14-deficient mice.
• Parp14 is expressed in macrophages and epithelial cells within mucosal tissues.
• Epithelial cells from infected Parp14-deficient mice showed a defective transcriptomic signature, including downregulation of ApoA1, Spink1, and Sst.

Conclusions:

• Parp14 is integral to the physiological response to Salmonella Typhimurium infection.
• Parp14 acts as a pleiotropic regulator of mucosal inflammation across multiple cell types.
• Parp14 plays a critical role in maintaining intestinal epithelial integrity and modulating immune responses during bacterial infection.