Abomasal RNA-seq reveals a strong local cell response of suckling lambs with resistance against Haemonchus contortus

Description

Santa Ines (SI) and Ile de France (IF) sheep are known to be resistant and susceptible to H. contortus infection, respectively. Several studies have shown some genes as potential biological markers for sheep resistance against gastrointestinal nematodes using molecular tools, including transcriptomic analysis. In this study, we sequenced the polyadenylated RNA of the abomasal tissue of SI and IF suckling lambs to identify mucosa-specific transcript alterations between breeds artificially infected with H. contortus. Naïve SI (n=4) and IF (n=4) lambs were artificially infected every other day, over a period of 52 days, from 14 to 66 days old, with a total of 5,400 H. contortus infective larvae. Fundic abomasal tissue samples were collected at 68 days old, and submitted to high-throughput RNA sequencing. Differential expression analysis (P value < 0.001 and FDR < 0.05) between SI and IF samples identified 292 genes, most of which showed greater expression in SI lambs. To help annotate and assign possible function to differentially expressed genes (DEGs), we used previously available single-cell RNAseq (scRNAseq) data from ovine abomasal mucosa to putatively identify cell types and possible mechanisms involved in resistance to H. contortus. In particular, genes associated with endothelial and tuft cells showed most increase in expression in SI relative to IF lambs. Santa Ines lambs had higher percentual of tuft cells than IF lambs in the fundic abomasal mucosa. Although we found innate immunity (cell mediated in mucosa) acting as protagonist for impairing H. contortus infection, a stronger acquired immune response was being modulated at an earlier stage by SI lambs. We suggest that the complex connection between innate and adaptive immunities are via cellular antigen processing and presentation (APP). Based on comparison with scRNAseq data, SI lambs showed a robust APP mechanism characterized mainly by greater T cell APP, macrophage differentiation, and cytokine signalling. We identified potential mechanisms and markers to advance knowledge for selection of H. contortus resistance at a very early age, in SI as well as in other commercial sheep breeds.

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