Contribution of the Immune Response in the Ileum to the Development of Diarrhoea caused by Helminth Infection: Studies with the Sheep Model

Gastrointestinal helminths are a global health issue, for humans as well as domestic animals. Most studies focus on the tissues that are infected with the parasite, but here we studied the ileum, a tissue that is rarely infected by helminths. We tested whether inflammation in the ileum contributes to the development and severity of diarrhoea, by comparing sheep that are susceptible (n = 4) or resistant (n = 4) to the disease. We analyzed the ileum transcriptome using RNASeq sequencing approach and various bioinformatics tools including FastQC, STAR, featureCounts, DESeq2, DAVID, clusterProfiler, Cytoscape (ClusterONE) and EnrichR. We identified 243 differentially expressed genes (DEGs), of which 118 were up-regulated and 125 were down-regulated DEGs in the diarrhoea-susceptible animals compared to the diarrhoea-resistant animals. The resulting DEGs were functionally enriched for biological processes, pathways and gene set enrichment analysis. The up-regulated DEGs suggested that an inflammatory immune response was coupled with genes involved in ‘Th2 immune response’ and ‘anti-inflammatory response’. The down-regulated DEGs were related to ion transport, muscle contraction and pathways preventing inflammation. We conclude that i) susceptibility to helminth-induced diarrhoea involves an inflammatory response at a non-infectious site; ii) down-regulation of pathways preventing inflammation can contribute to the severity of diarrhoea; and iii) genes involved in anti-inflammatory responses can reduce the inflammation and diarrhoea.