title: The Dermis as a Delivery Site of Trypanosoma brucei for Tsetse Flies.
abstract: Tsetse flies are the sole vectors of Trypanosoma brucei parasites that cause sleeping sickness. Our knowledge on the early interface between the infective metacyclic forms and the mammalian host skin is currently highly limited. Glossina morsitans flies infected with fluorescently tagged T. brucei parasites were used in this study to initiate natural infections in mice. Metacyclic trypanosomes were found to be highly infectious through the intradermal route in sharp contrast with blood stream form trypanosomes. Parasite emigration from the dermal inoculation site resulted in detectable parasite levels in the draining lymph nodes within 18 hours and in the peripheral blood within 42 h. A subset of parasites remained and actively proliferated in the dermis. By initiating mixed infections with differentially labeled parasites, dermal parasites were unequivocally shown to arise from the initial inoculum and not from a re-invasion from the blood circulation. Scanning electron microscopy demonstrated intricate interactions of these skin-residing parasites with adipocytes in the connective tissue, entanglement by reticular fibers of the periadipocytic baskets and embedment between collagen bundles. Experimental transmission experiments combined with molecular parasite detection in blood fed flies provided evidence that dermal trypanosomes can be acquired from the inoculation site immediately after the initial transmission. High resolution thermographic imaging also revealed that intradermal parasite expansion induces elevated skin surface temperatures. Collectively, the dermis represents a delivery site of the highly infective metacyclic trypanosomes from which the host is systemically colonized and where a proliferative subpopulation remains that is physically constrained by intricate interactions with adipocytes and collagen fibrous structures.
authors.affiliation: Unit of Veterinary Protozoology, Department of Biomedical Sciences, Institute of Tropical Medicine Antwerp (ITM), Antwerp, Belgium.|Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Wilrijk, Belgium.|Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, Ghent, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Caljon
authors.affiliation: Unit of Parasite Diagnostics, Department of Biomedical Sciences, Institute of Tropical Medicine Antwerp (ITM), Antwerp, Belgium.
authors.forename: Nick
authors.initials: N
authors.lastname: Van Reet
authors.affiliation: Unit of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium.|Structural Biology Research Center (SBRC), VIB, Brussels, Belgium.
authors.forename: Carl
authors.initials: C
authors.lastname: De Trez
authors.affiliation: Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Vermeersch
authors.affiliation: Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium.|Laboratory of Molecular Parasitology, Université Libre de Bruxelles (ULB), Gosselies, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Pérez-Morga
authors.affiliation: Unit of Veterinary Protozoology, Department of Biomedical Sciences, Institute of Tropical Medicine Antwerp (ITM), Antwerp, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van Den Abbeele
mesh_terms: D000818:Animals; D001733:Bites and Stings; D020405:Dermis / Q000469:parasitology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006790:Host-Parasite Interactions / Q000502:physiology*; D007303:Insect Vectors / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D014346:Trypanosoma brucei brucei; D014370:Tsetse Flies / Q000469:parasitology*