Pasteurella multocida causes liver pyroptosis in broilers through the MAPK-NLRP3-GSDMD signaling pathway

Area of Science:

• Veterinary Pathology
• Molecular Biology
• Immunology

Background:

• Avian cholera, caused by Pasteurella multocida (P. multocida), poses a significant threat to the poultry industry.
• Liver injury is a critical factor contributing to acute mortality in chickens infected with P. multocida.

Purpose of the Study:

• To elucidate the mechanisms by which P. multocida induces liver injury in broilers.
• To investigate the roles of pyroptosis, oxidative stress, and inflammation in P. multocida-induced liver damage.

Main Methods:

• Infection of 28-day-old broilers with P. multocida.
• Analysis of serum biochemical indicators, liver histopathology, oxidative stress markers, inflammatory cytokines, and pyroptosis-related proteins.
• Immunofluorescence and transcriptome analysis to identify key molecular pathways.

Main Results:

• P. multocida infection led to elevated liver enzymes (ALT, AST, T-Bil), necrosis, decreased antioxidant activities, and increased lipid peroxidation.
• Increased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-18, IFN-γ) and pyroptosis markers (NLRP3, Caspase-1, GSDMD) were observed.
• Transcriptome analysis revealed differential gene expression enriched in MAPK signaling pathways, confirming activation of oxidative stress, inflammation, and pyroptosis.

Conclusions:

• P. multocida infection triggers severe liver injury in broilers via pyroptosis, oxidative stress, and inflammation.
• The MAPK-NLRP3-GSDMD pathway plays a crucial role in P. multocida-induced liver damage.
• Identifying this pathway provides potential therapeutic targets for preventing and controlling avian cholera.