Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands

Abstract

Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response to Haemonchus infection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 × 10−4). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair, and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed.

Progress in the development of subunit vaccines for gastrointestinal nematodes of ruminants

“…In some of the cases cited above, one issue in the GIN vaccine trials performed thus far has been the issue of variability in immune responsiveness, both in challenged nonvaccinated and in vaccinated animals (46;52). This is not unique to ruminant GIN systems, and vaccine discovery programmes will need to take such variation in responsiveness into account; either by the testing of different adjuvant systems proposed to reduce lack of responsiveness in some individuals or by identifying protective components of the immune response in “responder” animals and subsequently incorporating components, in the vaccine per se or via a specific type of delivery system, that might help drive immune responses in an appropriate direction. For the GIN listed here, this type of work is in its infancy, but is being further developed under the PARAGONE vaccine programme using a “systems vaccinology” approach, whereby large‐scale transcriptomics studies are being undertaken in responding vs nonresponding vaccinated animals.…”

ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis

“…Only the uniquely mapped reads were used to count against the UCSC known gene annotation of mm9 to calculate the numbers of reads per gene. The counts of all samples were tabulated, then analyzed using DESeq ( 62 ) for normalization and identification of differentially expressed genes between the control and knockout samples using a standard workflow, as previously described ( 63 , 64 ). The Benjamini-Hochberg procedure ( 61 ) was used to correct for multiple hypothesis testing.…”

RNA‐Sequencing of ovine PBMC after exposure to Haemonchus contortus larval antigen

“…Guo et al identified wound healing genes upregulated in parasite resistant sheep during H contortus infection such as extracellular matrix, fibronectin and multiple collagen associated genes. Similarly, we found five matrix metalloproteinases to be upregulated in St. Croix PBMC in response to HcLA.…”

“…Comparative RNA‐sequencing (RNA‐Seq) was performed on abomasal mucosa of resistant CHB sheep and compared with a susceptible breed, Canaria Sheep (CS) 20 days after H contortus infection. Resistant CHB sheep were found to have 711 significantly upregulated genes after infection with H contortus, while CS sheep had 50 . The authors concluded CHB resistant sheep induced inflammatory responses faster as well as had increased complement activation, increased cell proliferation, genes associated with tissue repair and immune activation directed towards loss of parasite fecundity, all which contribute to H contortus resistance …”