scRNA-seq uncovers the transcriptional dynamics of Encephalitozoon intestinalis parasites in human macrophages
Pattana Jaroenlak1,2, Kacie L McCarty3,4, Bo Xia5
1Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
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.
Insights
Microsporidia parasites like Encephalitozoon intestinalis infect human macrophages, evading immune detection. This study reveals the parasite
Area of Science:
- Immunology
- Parasitology
- Microbiology
Background:
- Microsporidia are opportunistic intracellular parasites causing disease in humans.
- Encephalitozoon intestinalis infects the small intestine, with macrophages acting as potential reservoirs.
- Limited knowledge exists on macrophage response and parasite development during infection.
Purpose of the Study:
- To investigate the transcriptional changes in both Encephalitozoon intestinalis and human macrophages during in vitro infection.
- To understand the parasite's developmental program and the host's immune evasion strategies.
Main Methods:
- Single-cell RNA sequencing was employed to analyze host and parasite transcriptomes.
- In vitro infection model using human macrophages and E. intestinalis.
Main Results:
- Encephalitozoon intestinalis exhibits significant transcriptional shifts throughout its life cycle, outlining its developmental stages.
- A small subset of infected macrophages displayed an immune response, while most remained transcriptionally quiescent.
- The majority of parasites appear to evade host immune detection, utilizing macrophages for replication.
Conclusions:
- The study provides a detailed blueprint of E. intestinalis development within host cells.
- Findings suggest a stealthy parasitic lifestyle enabling macrophages to serve as replication reservoirs.
- Insights into the host-parasite interaction in primary human macrophages were gained.
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