title: Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum.
abstract: The obligate intracellular pathogen Leishmania major survives and multiplies in professional phagocytes. The evasion strategy to circumvent killing by host phagocytes and establish a productive infection is poorly understood. Here we report that the virulent inoculum of Leishmania promastigotes contains a high ratio of annexin A5-binding apoptotic parasites. This subpopulation of parasites is characterized by a round body shape, a swollen kinetoplast, nuclear condensation, and a lack of multiplication and represents dying or already dead parasites. After depleting the apoptotic parasites from a virulent population, Leishmania do not survive in phagocytes in vitro and lose their disease-inducing ability in vivo. TGF-beta induced by apoptotic parasites is likely to mediate the silencing of phagocytes and lead to survival of infectious Leishmania populations. The data demonstrate that apoptotic promastigotes, in an altruistic way, enable the intracellular survival of the viable parasites.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Lübeck, D-23538 Lübeck, Germany. zandbergen@uni-luebeck.de
authors.forename: Ger
authors.initials: G
authors.lastname: van Zandbergen
authors.forename: Annalena
authors.initials: A
authors.lastname: Bollinger
authors.forename: Alexander
authors.initials: A
authors.lastname: Wenzel
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.forename: Reinhard
authors.initials: R
authors.lastname: Voll
authors.forename: Matthias
authors.initials: M
authors.lastname: Klinger
authors.forename: Antje
authors.initials: A
authors.lastname: Müller
authors.forename: Christoph
authors.initials: C
authors.lastname: Hölscher
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: David
authors.initials: D
authors.lastname: Sacks
authors.forename: Werner
authors.initials: W
authors.lastname: Solbach
authors.forename: Tamás
authors.initials: T
authors.lastname: Laskay
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000032:analysis / Q000378:metabolism*; D017209:Apoptosis; D015536:Down-Regulation; D005260:Female; D018320:Leishmania major / Q000166:cytology* / Q000378:metabolism / Q000472:pathogenicity*; D007896:Leishmaniasis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010586:Phagocytes / Q000469:parasitology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation; D014774:Virulence
chemical_list: D017304:Annexin A5; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta