Title: Molecular networks associated with host resistance to gastrointestional nematodes in cattle Authors
Submitted to: Lecture
Publication Type: Abstract Only
Publication Acceptance Date: June 9, 2013
Publication Date: N/A
Technical Abstract: Parasitism by gastrointestinal nematodes is a disease severely affecting productivity in ruminants. To unravel mechanisms of host resistance to parasitic infection, we characterized the jejunal transcriptome of the cattle populations displaying resistance phenotypes in response to experimental Cooperia oncophora infection using RNAseq. Approximately 36.7 million of sequence reads (N=16) per sample were generated. The transcriptome was characterized using TopHat/Cuffdiff. The transcript abundance of 56 genes, such as intelectin 2 (ITLN2), and alkaline phosphatase, intestinal (ALPI), was significantly different between the resistant and susceptible cattle. The Gene Ontology terms (GO) significantly enriched among these genes were predominantly related to lipid metabolism. An algorithm for the reconstruction of accurate cellular networks (ARACNE) was used to infer de novo regulatory molecular networks in the Cooperia-jejunum interactome. Under a combined cutoff of an error tolerance (e = 0.10) and a stringent P-value threshold of mutual information (1.0 x 10-5), a total of 229, 100 direct interactions controlled by 20,288 hub genes were identified. Among these hub genes, 7,651 genes had = 100 direct neighbors while top 9,778 hub genes controlled more than 50% of total direct interactions. Three lysozymes (LYZ1, LYZ2, and LYZ3), strongly up-regulated at the mRNA level in resistant cattle, shared a common regulatory network of 55 genes and were probably co-regulated as they are located on bovine chromosome 5 in tandem. These ancient antimicrobials were likely involved in regulating host-parasite interactions. Notably, ALPI, known as a gut mucosal defense factor, controlled a molecular network consisting 410 genes, including 14 transcription factors and 10 genes in which expression was significantly regulated in resistant cattle. GO processes significantly enriched in the regulatory network controlled by STAT6 included lipid metabolism. Our findings provide insights into the immune regulation of host-parasite interactions and host resistance in cattle.