Nematode excretory-secretory (ES) products are essential for the establishment and maintenance of infections in mammals and are valued as therapeutic and diagnostic targets. While parasite effector proteins contribute to host immune evasion and anthelmintics have been shown to modulate secretory behaviors, little is known about the cellular origins of ES products or the tissue distributions of drug targets. We leveraged single-cell approaches in the human parasite Brugia malayi to generate an annotated cell expression atlas of microfilariae. We show that prominent antigens are transcriptionally derived from both secretory and non-secretory cell and tissue types, and anthelmintic targets display distinct expression patterns across neuronal, muscular, and other cell types. While the major classes of anthelmintics do not affect the viability of isolated cells at pharmacological concentrations, we observe cell-specific transcriptional shifts in response to ivermectin. Finally, we introduce a microfilariae cell culture model to enable future functional studies of parasitic nematode cells. We expect these methods to be readily adaptable to other parasitic nematode species and stages.
All data and scripts used for data analysis and visualization are publicly available at https://github.com/zamanianlab/Bmsinglecell-ms. Single-cell and FACS-pooled RNA-seq data has been deposited into NIH BioProjects PRJNA874113 and PRJNA874749.
Brugia malayi single-cell sequencingSRA BioProject, PRJNA874113.
Nematode FACS-pooled RNA-seqSRA BioProject, PRJNA874749.
The effect on anthelmintic drugs on Brugia malayi gene expression in vivoSRA BioProject, PRJNA388112.
- Mostafa Zamanian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Gáspár Jékely, Heidelberg University, Germany
© 2023, Henthorn et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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