Gene Co-Expression Network Analysis Identifies Genes Associated with Varying Responses to Salmonella Infection in Pigs

Salmonella enterica serovar Typhimurium is a gram-negative bacterium that can colonize the gut of several species of food producing farm animals to cause enteric or septicaemic salmonellosis. Besides compromising public health and food safety, sub-clinical salmonellosis is also believed to be a significant problem affecting the profitability of the pig industry. Here, we aimed to identify porcine genes and gene networks that differentiate distinct responses to Salmonella infection. Peripheral blood transcriptome profiles from 16 pigs belonging to extremes of the trait of faecal Salmonella shedding counts (low shedders (LS), n=8; persistent shedders (PS), n=8) were generated using RNA-sequencing from samples collected just before (day 0) and two days after (day 2) Salmonella inoculation. Weighted gene co-expression network analysis of day 0 samples identified four modules of co-expressed genes that significantly correlated with Salmonella shedding counts upon future infection. Two of those modules consisted largely of innate immunity related genes, many of which were significantly up-regulated at day 2 post infection. These modules also differed between LS and PS in network properties such as gene connectivity as well as in mean gene-wise expression levels. Genes within these modules include those previously reported to be involved in Salmonella resistance such as SLC11A1, TLR4 and CD14 as well as novel candidates like ARG2, TLR2, SIGLEC5, IGSF6 and TNFSF13B. The significantly higher connectivity and comparatively higher expression of genes within Salmonella shedding associated modules in LS than PS before infection may be factors contributing to the superior immune responses observed in LS upon infection.