Suppression of hyaluronidase reduces invasion and establishment of Haemonchus contortus larvae in sheep

Xiangshu Yang,Xiaochao Zhao,Sawar Khan,Jiayan Zhang,Ayesha Nisar,Xingang Feng

doi:10.1186/s13567-020-00831-8

Abstract

Haemonchus contortus is a hematophagous endoparasite of small ruminants, which is responsible for huge economic losses in livestock sector. Hyaluronidase produced by infective larvae of H. contortus can degrade hyaluronic acid present in the host’s abomasal tissue. Thus, it facilitates larval tissue invasion and early establishment. We herein explored this ability of hyaluronidase in H. contortus, and tested whether hyaluronidase is utilized as a virulence factor by H. contortus while establishing the infection. We first successfully blocked the hyaluronidase gene in L3 larvae by RNA interference (RNAi), which was subsequently confirmed by qPCR, enzymatic activity, and immunohistochemistry assays. Using these larvae we then conducted in vivo and in vitro assays on sheep to assess the effects of hyaluronidase suppression on larval invasion and establishment of infection. The in vivo assay showed a significant drop in worm burden in siRNA treated group in comparison to control group. During in vitro assay we applied an ovine ex vivo model where siRNA treated group of larvae showed significantly reduced invasion of the abomasal tissue explants as compared to control group. These findings indicate that hyaluronidase plays a key role in host’s tissue invasion and larval establishment, and it is used as a virulence factor by H. contortus while establishing the infection. As an invasive virulence molecule, its functional research is thus conducive to the prevention of haemonchosis.

Highlights

Haemonchus contortus is an important gastrointestinal parasitic nematode of domestic and wild small ruminants whose origin is traced back to an assemblage of antelopes in Africa during the late Tertiary period [1,2,3]
Silencing of hyaluronidase We explored the role of hyaluronidase in larval establishment of H. contortus infection
In order to block the production of hyaluronidase in infective L3 larvae, we applied the RNA interference (RNAi) to L3 larvae

Summary

Introduction

Haemonchus contortus is an important gastrointestinal parasitic nematode of domestic and wild small ruminants whose origin is traced back to an assemblage of antelopes in Africa during the late Tertiary period [1,2,3] It feeds on blood while living in the host’s abomasum and causes an infection called haemonchosis (a pathological condition characterized by anaemia, weight loss, and even mortality in infected animals), thereby leading to serious economic losses [4,5,6]. Invasion into the mucosa is a crucial step in larval establishment of H. contortus, and transition from a free-living to a parasitic life style takes place at this stage [26]. It could be a putative site for exploring new preventive and control strategies for haemonchosis. Not much is known about the mechanism and molecular mediators involved in larval establishment at this step

Methods

Results

Conclusion