title: Interactions with apoptotic but not with necrotic neutrophils increase parasite burden in human macrophages infected with Leishmania amazonensis.
abstract: Neutrophils are involved in the initial steps of most responses to pathogens. In the present study, we evaluated the effects of the interaction of apoptotic vs. necrotic human neutrophils on macrophage infection by Leishmania amazonensis. Phagocytosis of apoptotic, but not viable, neutrophils by Leishmania-infected macrophages led to an increase in parasite burden via a mechanism dependent on TGF-beta1 and PGE2. Conversely, infected macrophages' uptake of necrotic neutrophils induced killing of L. amazonensis. Leishmanicidal activity was dependent on TNF-alpha and neutrophilic elastase. Nitric oxide was not involved in the killing of parasites, but the interaction of necrotic neutrophils with infected macrophages resulted in high superoxide production, a process reversed by catalase, an inhibitor of reactive oxygen intermediate production. Initial events after Leishmania infection involve interactions with neutrophils; we demonstrate that phagocytosis of these cells in an apoptotic or necrotic stage can influence the outcome of infection, driving either parasite survival or destruction.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz-Fundação Oswaldo Cruz (CPqGM)- Fundação Oswaldo Cruz (FIOCRUZ), Salvador-BA, 40295-001, Brazil.
authors.forename: Lilian
authors.initials: L
authors.lastname: Afonso
authors.forename: Valéria M
authors.initials: VM
authors.lastname: Borges
authors.forename: Heloísa
authors.initials: H
authors.lastname: Cruz
authors.forename: Flávia L
authors.initials: FL
authors.lastname: Ribeiro-Gomes
authors.forename: George A
authors.initials: GA
authors.lastname: DosReis
authors.forename: Alberto Noronha
authors.initials: AN
authors.lastname: Dutra
authors.forename: Jorge
authors.initials: J
authors.lastname: Clarêncio
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Cláudia I
authors.initials: CI
authors.lastname: Brodskyn
mesh_terms: D000818:Animals; D017209:Apoptosis; D002374:Catalase / Q000494:pharmacology; D017281:Cost of Illness; D015232:Dinoprostone / Q000502:physiology; D006801:Humans; D007894:Leishmania mexicana / Q000472:pathogenicity / Q000502:physiology; D016773:Leishmaniasis, Cutaneous / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000469:parasitology*; D009336:Necrosis; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D010587:Phagocytosis; D013481:Superoxides / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: D053773:Transforming Growth Factor beta1; D013481:Superoxides; D002374:Catalase; D015232:Dinoprostone