scRNA-seq uncovers the transcriptional dynamics of Encephalitozoon intestinalis parasites in human macrophages

Pattana Jaroenlak, Kacie L. McCarty, Bo Xia, Cherry Lam, Erin E. Zwack, Nadia L. Almasri, Joseph Sudar, Maelle Aubry, Itai Yanai, Gira Bhabha () and Damian C. Ekiert ()
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Pattana Jaroenlak: Chulalongkorn University
Kacie L. McCarty: Johns Hopkins University
Bo Xia: Broad Institute of MIT and Harvard
Cherry Lam: New York University Grossman School of Medicine
Erin E. Zwack: New York University Grossman School of Medicine
Nadia L. Almasri: Johns Hopkins University
Joseph Sudar: NYU School of Medicine
Maelle Aubry: New York University Grossman School of Medicine
Itai Yanai: New York University Grossman School of Medicine
Gira Bhabha: New York University Grossman School of Medicine
Damian C. Ekiert: New York University Grossman School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Microsporidia are single-celled intracellular parasites that cause opportunistic diseases in humans. Encephalitozoon intestinalis is a prevalent human-infecting species that invades the small intestine. Macrophages are potential reservoirs of infection, and dissemination to other organ systems is also observed. The macrophage response to infection and the developmental trajectory of the parasite are not well studied. Here we use single cell RNA sequencing to investigate transcriptional changes in both the parasite and the host during E. intestinalis infection of human macrophages in vitro. The parasite undergoes large transcriptional changes throughout the life cycle, providing a blueprint for parasite development. While a small population of infected macrophages mount a response, most remain transcriptionally unchanged, suggesting that the majority of parasites may avoid host detection. The stealthy microsporidian lifestyle likely allows these parasites to harness macrophages for replication. Together, our data provide insights into the host response in primary human macrophages and the E. intestinalis developmental program.

Date: 2025
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DOI: 10.1038/s41467-025-57837-z

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