Background:
The integration of molecular data from hosts, parasites, and microbiota can enhance our understanding of the complex biological interactions underlying parasite resistance. Haemonchus contortus, the predominant sheep parasite species in the tropics, results in significant production and economic losses, which are further compounded by the diminishing efficiency of chemical control measures due to anthelmintic resistance. Knowledge of how the host responds to infection and how the parasite, in combination with microbiota effects, modulates host immunity can guide selection decisions to breed more resistant animals. This understanding can also refine management practices and inform the development of new therapeutics for long-term helminth control.
Results:
Egg per gram (EPG) counts were obtained in Morada Nova sheep subjected to two artificial infections with H. contortus, and used as a proxy to select animals with high resistance or susceptibility. The GAST, GNLY, IL13, MGRN1, FGF14, and RORC genes and transcripts were differentially expressed between groups based on RNA-seq of the abomasum. From 50K SNP genotyping, EPG heritability estimate was 0.12, and a genome-wide association study (GWAS) identified regions on chromosomes 2 and 11 harboring candidate genes for resistance, immune response, body weight, and adaptation. Trans-eQTLs between significant variants and differentially expressed transcripts were found. Amplicon sequence variants (ASVs) from PCR amplification and sequencing of bacterial and archaeal 16S rRNA genes in sheep feces and rumen generated functional co-expression modules correlated with resistance to H. contortus, showing enrichment in pathways of response to bacterium, immune and inflammatory responses, and hub features of the Christensenellaceae, Bacteroides, and Methanobrevibacter genera, Prevotellaceae family, and Verrucomicrobiota. In RNA-seq of H. contortus, some mitochondrial, collagen- and cuticle-related genes were expressed only in parasites retrieved from susceptible sheep.
Conclusions:
This study identified chromosome regions, genes, transcripts, and pathways involved in the elaborate interactions between the sheep host, its gastrointestinal microbiota and the H. contortus parasite. These findings can assist with the development of animal selection strategies for parasite resistance and interdisciplinary approaches to control H. contortus in sheep.
