Embrapa Pecuária Sudeste, São Carlos, SP, Brazil.
Munster Technological University, Cork, Ireland.
Parasit Vectors. 2024 Mar 1;17(1):102. doi: 10.1186/s13071-024-06205-9.
The integration of molecular data from hosts, parasites, and microbiota can enhance our understanding of the complex biological interactions underlying the resistance of hosts to parasites. Haemonchus contortus, the predominant sheep gastrointestinal parasite species in the tropics, causes significant production and economic losses, which are further compounded by the diminishing efficiency of chemical control owing to anthelmintic resistance. Knowledge of how the host responds to infection and how the parasite, in combination with microbiota, modulates host immunity can guide selection decisions to breed animals with improved parasite resistance. This understanding will help refine management practices and advance the development of new therapeutics for long-term helminth control.
Eggs per gram (EPG) of feces were obtained from Morada Nova sheep subjected to two artificial infections with H. contortus and used as a proxy to select animals with high resistance or susceptibility for transcriptome sequencing (RNA-seq) of the abomasum and 50 K single-nucleotide genotyping. Additionally, RNA-seq data for H. contortus were generated, and amplicon sequence variants (ASV) were obtained using polymerase chain reaction amplification and sequencing of bacterial and archaeal 16S ribosomal RNA genes from sheep feces and rumen content.
The heritability estimate for EPG was 0.12. GAST, GNLY, IL13, MGRN1, FGF14, and RORC genes and transcripts were differentially expressed between resistant and susceptible animals. A genome-wide association study identified regions on chromosomes 2 and 11 that harbor candidate genes for resistance, immune response, body weight, and adaptation. Trans-expression quantitative trait loci were found between significant variants and differentially expressed transcripts. Functional co-expression modules based on sheep genes and ASVs correlated with resistance to H. contortus, showing enrichment in pathways of response to bacteria, immune and inflammatory responses, and hub features of the Christensenellaceae, Bacteroides, and Methanobrevibacter genera; Prevotellaceae family; and Verrucomicrobiota phylum. In H. contortus, some mitochondrial, collagen-, and cuticle-related genes were expressed only in parasites isolated from susceptible sheep.
The present 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 will assist in the development of animal selection strategies for parasite resistance and interdisciplinary approaches to control H. contortus infection in sheep.
整合宿主、寄生虫和微生物组的分子数据可以增强我们对宿主抵抗寄生虫的复杂生物学相互作用的理解。旋毛虫是热带地区主要的绵羊胃肠道寄生虫，它会导致严重的生产和经济损失，而由于驱虫剂耐药性，化学控制的效率进一步降低。了解宿主如何对感染做出反应，以及寄生虫与微生物组相结合如何调节宿主免疫，可以指导选择具有改善寄生虫抗性的动物的决策。这种理解将有助于完善管理实践，并推进新的治疗方法的开发，以实现长期的寄生虫控制。
从接受两次旋毛虫人工感染的 Morada Nova 绵羊中获得每克粪便中的卵（EPG），并将其用作选择具有高抗性或易感性的动物进行胃转录组测序（RNA-seq）和 50K 单核苷酸基因分型的代理。此外，还生成了旋毛虫的 RNA-seq 数据，并通过对绵羊粪便和瘤胃液中的细菌和古菌 16S 核糖体 RNA 基因进行聚合酶链反应扩增和测序，获得了扩增子序列变异（ASV）。
EPG 的遗传力估计值为 0.12。GAST、GNLY、IL13、MGRN1、FGF14 和 RORC 基因和转录本在抗性和易感性动物之间存在差异表达。全基因组关联研究确定了包含抗性、免疫反应、体重和适应候选基因的染色体 2 和 11 上的区域。在显著变异和差异表达转录本之间发现了反式表达数量性状基因座。基于绵羊基因和 ASV 的功能共表达模块与抵抗旋毛虫有关，显示出对细菌、免疫和炎症反应以及 Christensenellaceae、Bacteroides 和 Methanobrevibacter 属、Prevotellaceae 科和 Verrucomicrobiota 门的反应途径的富集；旋毛虫中，一些与线粒体、胶原蛋白和角质层相关的基因仅在从易感性绵羊中分离的寄生虫中表达。
本研究鉴定了参与绵羊宿主、其胃肠道微生物组和旋毛虫寄生虫之间复杂相互作用的染色体区域、基因、转录本和途径。这些发现将有助于开发用于寄生虫抗性的动物选择策略，并促进控制绵羊旋毛虫感染的跨学科方法。
