Macrophages and dendritic cells have distinct transcriptome profiles during early infection with Salmonella Typhimurium

Salmonella enterica serovar Typhimurium is one of the most common foodborne pathogens that infect humans and cattle. It is zoonotic and causes similar symptoms in humans and cattle, mainly gut pathology and diarrhoea. Macrophages (MΦ) and dendritic cells (DC) are antigen-presenting cells (APC) which both play an important role in the immune response to Salmonella in human and bovine hosts. In this study we hypothesised that Salmonella Typhimurium may use different internalisation and survival strategies in DC and MФ. The Affymetrix bovine global microarray was used to examine the transcriptional response of Holstein-derived MΦ and DC infected with heatinactivated Salmonella (n=6), live Salmonella (n=6) and uninfected controls (n=6) during early infection (2 hours). Comparison of the transcriptome of non-infected cells with that of cells treated with heat-inactivated or live Salmonella revealed that MΦ and DC respond differently during early infection. 211 genes were differentially expressed in MΦ after treatment with live Salmonella (False Discovery Rate<0.05), whereas only 5 genes were differentially expressed in live Salmonella infected DC. Stimulation of DC with heat-inactivated Salmonella induced a great number of gene expression changes than live bacteria (33). However, the reverse trend was observed in MΦ, with heat-inactivated bacteria inducing differential expression in fewer genes than live bacteria (115). Greater upregulation of proinflammatory cytokines (e.g. IL-6, IL-1β) was observed in MΦ than in DC. The transcriptome analysis also identified Pyrin as a novel gene involved in Salmonella infection. This gene, previously only linked with Familial Mediterranean Fever in humans, showed strong up regulation following Salmonella stimulation in both MΦ and DC. Our study provides novel genome wide transcriptional profiling data on the early response of MΦ and DC to S. Typhimurium. Comparison of the early response of these two APC to Salmonella clearly showed that S. Typhimurium infection elicits a greater transcriptional response in MΦ than DC.