Transcriptomic and cellular profile of the local immune response to artificial infection by Haemonchus contortus in lambs of different breeds and resistance phenotypes

• Grant number: 24/02589-6
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2024
• End date: October 31, 2026
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Preventive Veterinary Medicine
• Principal Investigator: Ana Claudia Alexandre de Albuquerque
• Grantee: Ana Claudia Alexandre de Albuquerque
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Associated researchers: Adriana Mércia Guaratini Ibelli ; Alessandro Pelegrine Minho ; Ana Carolina de Souza Chagas ; Cintia Hiromi Okino ; Hornblenda Joaquina Silva Bello ; Raquel Rubia Rech ; Sergio Novita Esteves ; Simone Cristina Méo Niciura

Abstract

Sheep production is directly affected by Haemonchus contortus infection, the main parasite species in tropical and subtropical regions, which is responsible for significant economic losses in sheep production. The emergence of populations with multiple resistances to anthelmintics threatens the sustainable production of small ruminants. The current scenario requires an effort to mitigate the problem. The selection of resistant animals together with parasite replacement are sustainable control measures that aim to reduce the parasite burden and environmental contamination with nematode larvae, increase productivity, reduce economic losses, and preserve the effectiveness of anthelmintics. Parasite replacement is being widely studied within the Thematic Project "Parasite-host-environment approach to control anthelmintic resistance in sheep herds" (Process: 2021/02535-5) concerning the process of reversing resistance through tests in vivo, in vitro, and molecular, as well as the differentiation of animals of different breeds by b-globin haplotypes. In addition to proposed in the aforementioned project, it is proposed to analyze and compare the immunological mechanisms involved in the response to infection by H. contortus in different sheep breeds, Santa Inês, Texel, and White Dorper, and different b-globin haplotypes, through the RNA-seq transcriptome profile, and cells through immunohistochemistry and histopathological analysis to identify more resistant individuals. Thirty 6- to 7-month-old males, each of the breeds aforementioned, from each breeding season (2022, 2023 and 2024), will be selected by b-globin haplotypes and subsequently individually infected with 4,000 H. contortus third-stage larvae (L3) and monitored for 28 days. After slaughter, parasite specimens will be collected for measurement, as well as egg counting in females. Fragments of the abomasal tissue will be collected for RNA extraction and transcriptome analysis to perform immune response cells marking via immunohistochemistry, histopathological analysis, and effector cell counting. Thus, it is expected that by elucidating the different cellular and molecular mechanisms involved in the local immunological response, it will be possible to select resistant animals via genetic biomarkers as a sustainable method for controlling H. contortus. (AU)