Comparative Analysis of Salmonella typhimurium ‐Induced Transcriptomic Changes in the Spleen of Beijing‐You Chickens and Guang Ming Broilers

Avian salmonellosis, caused by Salmonella species, represents a significant zoonotic disease that substantially impacts both the poultry industry and public health security. Although domestic poultry breeds exhibit distinct interbreed variations in resistance to Salmonella typhimurium (ST) infection, the underlying molecular mechanisms remain poorly understood. In this study, we employed integrated immunophenotypic (including H/L ratio, IFN‐γ, IL‐1β, and IL‐8) and splenic transcriptomic analyses to identify candidate genes associated with differential resistance to Salmonella infection across chicken breeds. To this end, 28‐day‐old Guang Ming No. 2 broiler line B (GM) and Beijing‐You (BY) chickens were challenged with Salmonella typhimurium (ST) at a dose of 2.5 × 10 10 CFU/mL. Through an integrated approach combining differential expression analysis and WGCNA, we identified three key candidate genes— EGR1 , FOS , and DUSP1 —associated with differential resistance to Salmonella infection between chicken breeds. Functional validation confirmed that FOS and DUSP1 play significant roles in modulating immune cell responses to ST infection. Furthermore, we uncovered a novel regulatory mechanism whereby EGR1 negatively regulates DUSP1 . These findings provide potential candidate targets for poultry disease resistance research.