PT  - JOURNAL ARTICLE
AU  - Christian Reuter
AU  - Fabian Imdahl
AU  - Laura Hauf
AU  - Ehsan Vafadarnejad
AU  - Philipp Fey
AU  - Tamara Finger
AU  - Heike Walles
AU  - Antoine-Emmanuel Saliba
AU  - Florian Groeber-Becker
AU  - Markus Engstler
TI  - Vector-borne <em>Trypanosoma brucei</em> parasites develop in artificial human skin and persist as skin tissue forms
AID  - 10.1101/2021.05.13.443986
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.13.443986
4099  - http://biorxiv.org/content/early/2021/05/13/2021.05.13.443986.short
4100  - http://biorxiv.org/content/early/2021/05/13/2021.05.13.443986.full
AB  - 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. In the skin, the metacyclic parasites reactivate and differentiate into proliferative trypanosomes before colonizing the host’s blood and tissues. We generated an advanced human skin equivalent and used tsetse flies to naturally infect the artificial skin with trypanosomes. We detailed the chronological order of the parasites’ development in the skin, and found a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Single-cell parasite transcriptomics were used to document the biological events during differentiation and host invasion at five different timepoints. After the establishment of a proliferative trypanosome population in the skin, the parasites entered a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We termed these quiescent trypanosomes skin tissue forms (STF), a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals.Competing Interest StatementThe authors have declared no competing interest.