Cell Death and Transcriptional Responses Induced in Larvae of the Nematode <i>Haemonchus contortus</i> by Toxins/Toxicants with Broad Phylogenetic Efficacy

• Main Authors: Douglas P. Jasmer, Bruce A. Rosa, Makedonka Mitreva
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Pharmaceuticals
• Subjects: nematode; intestine; anthelmintics; microscopy; pathology; RNA-seq
• Online Access: https://www.mdpi.com/1424-8247/14/7/598

Establishing methods to investigate treatments that induce cell death in parasitic nematodes will promote experimental approaches to elucidate mechanisms and to identify prospective anthelmintics capable of inducing this outcome. Here, we extended recent progress on a method to monitor cell death and to identify small molecule inhibitors in <i>Ascaris suum</i> to <i>Haemonchus contortus</i>, a phylogenetically distant parasitic nematode of significance for both human and agricultural animal health. We utilized a diverse group of small molecule inhibitors referred to as nematode intestinal toxins/toxicants (NITs) coupled with motility, cytological and cell death assays to resolve gross effects on motility and individual cells and organ systems of two <i>H. contortus</i> larval stages in culture. Early transcriptional response evaluation identified NIT-responsive genes and pathways. The scope of death among cells in larvae varied among NITs but shared patterns with <i>A. suum</i>, despite the approach having some limitations due to characteristics of <i>H. contortus</i> larvae. Gene response patterns varied among NITs tested and provided information on the cell targets and pathways affected. Experimental NIT assays provide tools capable of inducing cell death in larval stages of parasitic nematodes, and can resolve many individual cells and organ systems in which cell death can be induced.