Resolving the origins of secretory products and anthelmintic responses in a human parasitic nematode at single-cell resolution

Abstract
Data availability
Article and author information
Metrics

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.

The following data sets were generated

1. Henthorn and Zamanian
(2022) Brugia malayi single-cell sequencing
SRA BioProject, PRJNA874113.

https://www.ncbi.nlm.nih.gov/bioproject/PRJNA874113
1. Henthorn and Zamanian
(2022) Nematode FACS-pooled RNA-seq
SRA BioProject, PRJNA874749.

https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA874749

The following previously published data sets were used

1. Reaves BJ et al
(2017) The effect on anthelmintic drugs on Brugia malayi gene expression in vivo
SRA BioProject, PRJNA388112.

https://www.ncbi.nlm.nih.gov/bioproject/PRJNA388112

Article and author information

Author details

Clair R Henthorn

Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Paul M Airs

Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Emma K Neumann

Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Mostafa Zamanian

Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, United States

For correspondence
mzamanian@wisc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9233-1760

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.

Copyright

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.