Resolving the origins of secretory products and anthelmintic responses in a human parasitic nematode at single-cell resolution
- University of Wisconsin-Madison, United States
Abstract
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.
Data availability
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.
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Brugia malayi single-cell sequencingSRA BioProject, PRJNA874113.
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Nematode FACS-pooled RNA-seqSRA BioProject, PRJNA874749.
Article and author information
Author details
Funding
National Institutes of Health (R01 AI151171)
- Mostafa Zamanian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gáspár Jékely, Heidelberg University, Germany
Version history
- Preprint posted: August 30, 2022 (view preprint)
- Received: August 31, 2022
- Accepted: June 9, 2023
- Accepted Manuscript published: June 15, 2023 (version 1)
- Version of Record published: July 4, 2023 (version 2)
Copyright
© 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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Resolving the origins of secretory products and anthelmintic responses in a human parasitic nematode at single-cell resolution
eLife 12:e83100.
https://doi.org/10.7554/eLife.83100
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