Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms

Christian Reuter, Laura Hauf, Fabian Imdahl, Rituparno Sen, Ehsan Vafadarnejad, Philipp Fey, Tamara Finger, Nicola G. Jones, Heike Walles, Lars Barquist, Antoine-Emmanuel Saliba, Florian Groeber-Becker and Markus Engstler ()
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Christian Reuter: Biocenter, Julius-Maximilians-Universitaet of Wuerzburg
Laura Hauf: Biocenter, Julius-Maximilians-Universitaet of Wuerzburg
Fabian Imdahl: Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI)
Rituparno Sen: Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI)
Ehsan Vafadarnejad: Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI)
Philipp Fey: Translational Center Regenerative Therapies, Fraunhofer ISC
Tamara Finger: Translational Center Regenerative Therapies, Fraunhofer ISC
Nicola G. Jones: Biocenter, Julius-Maximilians-Universitaet of Wuerzburg
Heike Walles: Translational Center Regenerative Therapies, Fraunhofer ISC
Lars Barquist: Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI)
Antoine-Emmanuel Saliba: Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI)
Florian Groeber-Becker: University Hospital Wuerzburg
Markus Engstler: Biocenter, Julius-Maximilians-Universitaet of Wuerzburg

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Transmission of Trypanosoma brucei by tsetse flies involves the deposition of the cell cycle-arrested metacyclic life cycle stage into mammalian skin at the site of the fly’s bite. We introduce an advanced human skin equivalent and use tsetse flies to naturally infect the skin with trypanosomes. We detail the chronological order of the parasites’ development in the skin by single-cell RNA sequencing and find a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Here we show that after the establishment of a proliferative population, the parasites enter a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We term these quiescent trypanosomes skin tissue forms, a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals.

Date: 2023
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DOI: 10.1038/s41467-023-43437-2

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