title: Mimicry of apoptotic cells by exposing phosphatidylserine participates in the establishment of amastigotes of Leishmania (L) amazonensis in mammalian hosts.
abstract: Signaling through exposed phosphatidylserine (PS) is fundamental for the TGFbeta1-dependent, noninflammatory phagocytosis of apoptotic cells. This same mechanism operates in the internalization of amastigotes of Leishmania (L) amazonensis (L(L)a) in a process quoted as apoptotic mimicry. Now we show that the host modulates PS exposure by the amastigotes and, as a consequence, BALB/c mice-derived amastigotes expose significantly more PS than those derived from C57BL/6 mice. Due to this difference in the density of surface PS molecules, the former are significantly more infective than the latter, both in vivo, in F1 (BALB/c x C57BL/6) mice, and in vitro, in thioglycollate-derived macrophages from this same mouse strain. PS exposure increases with progression of the lesion and reaches its maximum value in amastigotes obtained at the time point when the lesion in C57BL/6 mice begins to decrease in size and the lesions in BALB/c mice are still growing in size. Synthesis of active TGFbeta1, induction of IL-10 message, and inhibition of NO synthesis correlate with the amount of surface PS displayed by viable (propidium iodide-negative) infective amastigote. Furthermore, we also show that, similar to what happens with apoptotic cells, amastigotes of L(L)a are internalized by macropinocytosis. This mechanism of internalization is consistent with the large phagolysosomes characteristic of L(L)a infection. The intensity of macrophage macropinocytic activity is dependent on the amount of surface PS displayed by the infecting amastigote.
authors.affiliation: Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Cāncer, Rio de Janeiro, Brazil.
authors.forename: João L M
authors.initials: JL
authors.lastname: Wanderley
authors.forename: Maria E C
authors.initials: ME
authors.lastname: Moreira
authors.forename: Aline
authors.initials: A
authors.lastname: Benjamin
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Bonomo
authors.forename: Marcello A
authors.initials: MA
authors.lastname: Barcinski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D006790:Host-Parasite Interactions / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007894:Leishmania mexicana / Q000254:growth & development* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000378:metabolism*; D010873:Pinocytosis / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D010718:Phosphatidylserines; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D009569:Nitric Oxide