Genome-Wide Transcriptomic Analysis of Intestinal Tissue to Assess the Impact of Nutrition and a Secondary Nematode Challenge in Lactating Rats

Abstract

BackgroundGastrointestinal nematode infection is a major challenge to the health and welfare of mammals. Although mammals eventually acquire immunity to nematodes, this breaks down around parturition, which renders periparturient mammals susceptible to re-infection and an infection source for their offspring. Nutrient supplementation reduces the extent of periparturient parasitism, but the underlying mechanisms remain unclear. Here, we use a genome wide approach to assess the effects of protein supplementation on gene expression in the small intestine of periparturient rats following nematode re-infection.Methodology/Principal FindingsThe use of a rat whole genome expression microarray (Affymetrix Gene 1.0ST) showed significant differential regulation of 91 genes in the small intestine of lactating rats, re-infected with Nippostrongylus brasiliensis compared to controls; affected functions included immune cell trafficking, cell-mediated responses and antigen presentation. Genes with a previously described role in immune response to nematodes, such as mast cell proteases, and intelectin, and others newly associated with nematode expulsion, such as anterior gradient homolog 2 were identified. Protein supplementation resulted in significant differential regulation of 64 genes; affected functions included protein synthesis, cellular function and maintenance. It increased cell metabolism, evident from the high number of non-coding RNA and the increased synthesis of ribosomal proteins. It regulated immune responses, through T-cell activation and proliferation. The up-regulation of transcription factor forkhead box P1 in unsupplemented, parasitised hosts may be indicative of a delayed immune response in these animals.Conclusions/SignificanceThis study provides the first evidence for nutritional regulation of genes related to immunity to nematodes at the site of parasitism, during expulsion. Additionally it reveals genes induced following secondary parasite challenge in lactating mammals, not previously associated with parasite expulsion. This work is a first step towards defining disease predisposition, identifying markers for nutritional imbalance and developing sustainable measures for parasite control in domestic mammals.

Proteomic analysis of the abomasal mucosal response following infection by the nematode, Haemonchus contortus, in genetically resistant and susceptible sheep

“…Consistent with this observation is our recent finding that the satiety peptide ghrelin is also differentially expressed between the resistant and susceptible sheep, even in the nematode naïve sheep [39]. In another study, genes associated with the expulsion of nematodes were also shown to be regulated by nutritional status [40]. The network developed from the susceptible animal is quite different and is arranged around the cytokines IL4 and IFNγ, although these cytokines were not themselves identified in this study.…”

Molecular cloning and characterisation of ovine dual oxidase 2

“…Four weeks after the secondary challenge, DUOX2 expression had continued to increase, while DUOXA2 expression had plateaued. These results have recently been supported by studies from other research groups who found a rapid escalation in both DUOX2 and DUOXA2 gene expression in the small intestine of cattle infected with Cooperia oncophora (Li and Gasbarre, 2009), and similarly elevation of DUOX2 in the small intestine of mice infected with Nippostrongylus brasiliensis (Athanasiadou et al, 2011).…”

Dual Oxidases Control Release of Hydrogen Peroxide by the Gastric Epithelium to Prevent Helicobacter felis Infection and Inflammation in Mice

“…In our chronic infection model, loss of active DUOX enzymes led to increased mucosal colonization and exacerbated, yet futile, chronic inflammatory response. The subunits of the DUOX2 isoenzyme have been identified among the highest induced genes in Crohn’s disease 11,12 , irritable bowel syndrome 13 , and infectious diseases 14,47 . It remains to be shown whether loss of DUOX activity will also exacerbate other infectious or chronic inflammatory conditions of the luminal GI tract in which DUOX was found to be activated.…”