Interactions with apoptotic but not with necrotic neutrophils increase parasite burden in human macrophages infected with Leishmania amazonensis.
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.
Afonso
Lilian
L
Centro de Pesquisas Gonçalo Moniz-Fundação Oswaldo Cruz (CPqGM)- Fundação Oswaldo Cruz (FIOCRUZ), Salvador-BA, 40295-001, Brazil.
Borges
Valéria M
VM
Cruz
Heloísa
H
Ribeiro-Gomes
Flávia L
FL
DosReis
George A
GA
Dutra
Alberto Noronha
AN
Clarêncio
Jorge
J
de Oliveira
Camila I
CI
Barral
Aldina
A
Barral-Netto
Manoel
M
Brodskyn
Cláudia I
CI
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
D053773:Transforming Growth Factor beta1; D013481:Superoxides; D002374:Catalase; D015232:Dinoprostone