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

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 Ascaris suum to Haemonchus contortus, 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 H. contortus 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 A. suum, despite the approach having some limitations due to characteristics of H. contortus 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.

Automated summary

Establishing methods to investigate treatments inducing cell death in parasitic nematodes is crucial for developing experimental approaches to understand mechanisms and identify potential anthelmintics. The study extended progress on monitoring cell death in Ascaris suum to Haemonchus contortus, revealing varied effects of small molecule inhibitors on cell death in different nematode larvae stages. This research provides insights into the potential targets and pathways affected by small molecule inhibitors, highlighting the importance of experimental assays in inducing cell death in parasitic nematodes.