Single-cell RNA-seq reveals CD16^-monocytes as key regulators of human monocyte transcriptional response to<i>Toxoplasma</i>

ABSTRACT Monocytes are among the major myeloid cells that respond toToxoplasma, a ubiquitous foodborne that infects ≥1 billion people worldwide, in human peripheral blood. As such, a molecular understanding of human monocyte-Toxoplasmainteractions can expedite the development of novel human toxoplasmosis control strategies. Current molecular studies on monocyte-Toxoplasmainteractions are based on average cell or parasite responses across bulk cell populations. Although informative, population-level averages of monocyte responses toToxoplasmahave sometimes produced contradictory results, such as whether CCL2 or IL12 define effective monocyte response to the parasite. Here, we used single-cell dual RNA sequencing (scDual-Seq) to comprehensively define, for the first time, the monocyte and parasite transcriptional responses that underpin human monocyte-Toxoplasmaencounters at the single cell level. We report extreme transcriptional variability between individual monocytes. Furthermore, we report thatToxoplasma-exposed and unexposed monocytes are transcriptionally distinguished by a reactive subset of CD14++CD16-monocytes. Functional cytokine assays on sorted monocyte populations show that the infection-distinguishing monocytes secrete high levels of chemokines, such as CCL2 and CXCL5. These findings uncover theToxoplasma-induced monocyte transcriptional heterogeneity and shed new light on the cell populations that largely define cytokine and chemokine secretion in human monocytes exposed toToxoplasma..

Medienart:	Preprint

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	bioRxiv.org - (2023) vom: 23. Sept. Zur Gesamtaufnahme - year:2023

Sprache:	Englisch

Beteiligte Personen:	Patir, Anirudh [VerfasserIn] Gossner, Anton [VerfasserIn] Ramachandran, Prakash [VerfasserIn] Alves, Joana [VerfasserIn] Freeman, Tom C. [VerfasserIn] Henderson, Neil C. [VerfasserIn] Watson, Michael [VerfasserIn] Hassan, Musa A. [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	570 Biology

doi:	10.1101/863274

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PPN (Katalog-ID):	XBI000780898