title: Exosome Secretion by the Parasitic Protozoan Leishmania within the Sand Fly Midgut.
abstract: Despite several studies describing the secretion of exosomes by Leishmania in vitro, observation of their formation and release in vivo has remained a major challenge. Herein, we show that Leishmania constitutively secretes exosomes within the lumen of the sand fly midgut through a mechanism homologous to the mammalian pathway. Through egestion experiments, we demonstrate that Leishmania exosomes are part of the sand fly inoculum and are co-egested with the parasite during the insect's bite, possibly influencing the host infectious process. Indeed, co-inoculation of mice footpads with L. major plus midgut-isolated or in-vitro-isolated L. major exosomes resulted in a significant increase in footpad swelling. Notably, co-injections produced exacerbated lesions through overinduction of inflammatory cytokines, in particular IL-17a. Our data indicate that Leishmania exosomes are an integral part of the parasite's infectious life cycle, and we propose to add these vesicles to the repertoire of virulence factors associated with vector-transmitted infections.
authors.affiliation: Department of Medicine, Microbiology and Immunology, McGill University, 3775 University Street, Montréal, QC H3A 2B4, Canada; Infectious Diseases and Immunity in Global Heath Program, Research Institute of the McGill University Health Centre, 1001 Boulevard Décarie, Montréal, QC H4A 3J1, Canada.
authors.forename: Vanessa Diniz
authors.initials: VD
authors.lastname: Atayde
authors.affiliation: Vector Molecular Biology Section, NIH, 12735 Twinbrook Parkway, Rockville, MD 20878, USA; Faculty of Health Science, Selahaddin Eyyubi University, 215 Ba?c?lar Mah. ?anl?urfa Blv Otogar Kar??s?, Diyarbakir, 21090 Ba?lar, Turkey.
authors.forename: Hamide
authors.initials: H
authors.lastname: Aslan
authors.affiliation: Vector Molecular Biology Section, NIH, 12735 Twinbrook Parkway, Rockville, MD 20878, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Townsend
authors.affiliation: Department of Medicine, Microbiology and Immunology, McGill University, 3775 University Street, Montréal, QC H3A 2B4, Canada.
authors.forename: Kasra
authors.initials: K
authors.lastname: Hassani
authors.affiliation: Vector Molecular Biology Section, NIH, 12735 Twinbrook Parkway, Rockville, MD 20878, USA. Electronic address: skamhawi@niaid.nih.gov.
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.affiliation: Department of Medicine, Microbiology and Immunology, McGill University, 3775 University Street, Montréal, QC H3A 2B4, Canada; Infectious Diseases and Immunity in Global Heath Program, Research Institute of the McGill University Health Centre, 1001 Boulevard Décarie, Montréal, QC H4A 3J1, Canada. Electronic address: martin.olivier@mcgill.ca.
authors.forename: Martin
authors.initials: M
authors.lastname: Olivier
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D007422:Intestines / Q000469:parasitology*; D007891:Leishmania / Q000378:metabolism / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D011576:Psychodidae / Q000469:parasitology*
chemical_list: D016207:Cytokines