Messenger RNA Sequencing and Pathway Analysis Provide Novel Insights Into the Susceptibility to Salmonella enteritidis Infection in Chickens

Salmonella enteritidis (SE) is a foodborne pathogen that negatively affects both animal and human health. Controlling poultry SE infection will have great practical significance for human public health, as poultry are considered to be important sources and carriers of the disease. In this study, the splenic transcriptomes of challenged-susceptible (S), challenged-resistant (R) and non-challenged (C) chicks (3-days old, specific-pathogenfree White Leghorn) were characterized in order to identify the immune-related gene markers and pathways. A total of 934 significant differentially expressed genes (DEGs) were identified in comparisons among the C, R and S birds. 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 will 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.