A total of 934 significant differentially expressed genes (DEGs) were identified in comparisons among the C, R and S birds using RNA sequencing. First reported here, the DEGs involved in the Forkhead box O (FoxO) signaling pathway, especially FoxO3, were identified as potential markers for host resistance to SE infection. The challenged-susceptible birds exhibited strong activation of the FoxO signaling pathway, which may be a major defect causing immune cell apoptosis as part of SE-induced pathology; these S birds also showed weak activation of mitogen-activated protein kinase (MAPK)-related genes, contrasting with strong splenic activation in the R birds. Interestingly, suppression of several pathways in the immune response against Salmonella, including cytokine-cytokine receptor interaction and Jak-STAT, was only found in S birds and there was evidence of cross-talk among these pathways, perhaps contributing to susceptibility to Salmonella infection.
These findings help facilitate understanding resistance and susceptibility to SE infection in the earliest phases of the host immune response through Salmonella-induced pathways, provide new approaches to develop strategies for SE prevention and treatment and may enhance innate resistance by genetic selection in animals.