Transcriptome profiling analysis of caeca in chicks challenged with Salmonella Typhimurium reveals differential expression of genes involved in host mucosal immune response.

Temporal regulation of global gene expression in the caeca of chickens infected with Salmonella Typhimurium has not been investigated previously. In this study, we performed the transcriptome analysis of the caeca of Salmonella Typhimurium challenged chicks to understand the regulation of the mucosal immune system in a temporal manner. The Salmonella infection resulted in the activation of the caecal immune system by the upregulation of the differentially expressed genes (DEGs; false discovery rate (FDR) < 0.05; log2 fold change > 1) involved in biological pathways such as Toll-like receptor signaling pathway, Salmonella infection, cytokine-cytokine receptor interaction, phagosome, apoptosis and intestinal immune network for IgA production. The activation of biological pathways such as RIG-I-like receptor signaling pathway, ErbB signaling pathway and cellular senescence showed a time-dependent response of the host immune system. A 49% increase in the DEGs on day 7 compared with day 3 post-infection (p.i.) suggested a time-dependent role of multiple genes such as AvBD1, AvBD2, AvBD7, IL2, IL10, IL21, SIVA1, CD5, CD14 and GPR142 in the regulation of the immune system. Nested network analysis of the individual biological pathways showed that IL6 played a significant role in the immune system regulation by activating the pathways, including Toll-like receptor signaling pathway, Salmonella infection, intestinal immune network for IgA production and C-type lectin receptor signaling pathway. The downregulated DEGs (FDR < 0.05; log2 fold change < -1) showed that Salmonella challenge affected the functions of pathways, such as tryptophan metabolism, retinol metabolism, folate biosynthesis and pentose and glucoronate interconversions, suggesting the disruption of cellular mechanisms involved in nutrient synthesis, absorption and metabolism. Overall, the immune response was temporally regulated through the activation of Toll-like signaling receptor pathway, cytokine-cytokine interactions and Salmonella infection, where IL6 played a significant role in the modulation of caecal immune system against Salmonella Typhimurium. KEY POINTS: • The immune response to Salmonella Typhimurium challenge was temporally regulated in the caeca of chickens. • Many newly identified genes have been shown to be involved in the activation of the immune system. • Toll-like receptors and interleukins played a key role in immune system regulation.