ORIGINAL RESEARCH article

Front. Immunol.

Sec. Parasite Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1582645

This article is part of the Research TopicMolecular Mechanisms of the Host Immune Response to Toxoplasma gondii InfectionView all 5 articles

Dual single-cell and bulk RNA sequencing reveal transcriptional profiles underlying heterogenous host-parasite interactions in human peripheral blood mononuclear cells

Provisionally accepted
  • 1Roslin Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom
  • 2Lancaster University, Lancaster, England, United Kingdom

The final, formatted version of the article will be published soon.

Toxoplasma gondii, a zoonotic apicomplexan that infects over a billion people worldwide, can cause early death in immunocompromised individuals and defects in foetal brain development. Toxoplasma is also a major cause of abortion in small ruminants. When Toxoplasma encounters host cells, several outcomes are possible. For example, the parasite can enter the host cell or can inject its effector proteins into the cell without entering. These heterogenous outcomes occur simultaneously in the same host and likely determine disease pathogenesis. Yet, current knowledge of host-Toxoplasma interactions is largely based on averaged responses in bulk cell populations. Here, we employed single cell RNA (scRNA) and bulk RNA sequencing to investigate the transcriptional profiles that underpin heterogenous host-Toxoplasma interaction in human peripheral blood mononuclear cells. We observed that Toxoplasma preferentially infects and elicits transcriptional responses in dendritic cells in human blood. Additionally, we observed that monocytes adopt a dendritic cell-like transcriptional profile over the course of infection. Using genes expressed in sorted host cell populations representative of the different heterogenous host-Toxoplasma interaction outcomes as a reference panel, we show that genes expressed in cells infected via phagocytosis are largely expressed in dendritic cells. Thus, by integrating scRNA and bulk RNA sequencing, our study unveils the transcriptional profiles of diverse Toxoplasma-host cell interaction outcomes, providing novel avenues for targeted investigations into host gene functions during Toxoplasma infections.

Keywords: Toxoplasma gondii, Host-Pathogen Interactions, PBMCs, Monocytes, Dendritic Cells, single-cell RNA sequencing

Received: 24 Feb 2025; Accepted: 28 May 2025.

Copyright: © 2025 R G Chandrasegaran, Shih and Hassan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Praveena R G Chandrasegaran, Roslin Institute, University of Edinburgh, Edinburgh, EH25 9RG, Scotland, United Kingdom

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