Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps.
Neutrophils are short-lived leukocytes that die by apoptosis, necrosis, and NETosis. Upon death by NETosis, neutrophils release fibrous traps of DNA, histones, and granule proteins named neutrophil extracellular traps (NETs), which can kill bacteria and fungi. Inoculation of the protozoan Leishmania into the mammalian skin causes local inflammation with neutrophil recruitment. Here, we investigated the release of NETs by human neutrophils upon their interaction with Leishmania parasites and NETs' ability to kill this protozoan. The NET constituents DNA, elastase, and histones were detected in traps associated to promastigotes by immunofluorescence. Electron microscopy revealed that Leishmania was ensnared by NETs released by neutrophils. Moreover, Leishmania and its surface lipophosphoglycan induced NET release by neutrophils in a parasite number- and dose-dependent manner. Disruption of NETs by DNase treatment during Leishmania-neutrophil interaction increased parasite survival, evidencing NETs' leishmanicidal effect. Leishmania killing was also elicited by NET-rich supernatants from phorbol 12-myristate 13-acetate-activated neutrophils. Immunoneutralization of histone during Leishmania-neutrophil interaction partially reverted Leishmania killing, and purified histone killed the parasites. Meshes composed of DNA and elastase were evidenced in biopsies of human cutaneous leishmaniasis. NET is an innate response that might contribute to diminish parasite burden in the Leishmania inoculation site.
Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, Bloco I, 21941-902, Rio de Janeiro, Brazil.
Anderson B
AB
Guimarães-Costa
Michelle T C
MT
Nascimento
Giselle S
GS
Froment
Rodrigo P P
RP
Soares
Fernanda N
FN
Morgado
Fátima
F
Conceição-Silva
Elvira M
EM
Saraiva
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000276:immunology*; D006028:Glycosphingolipids / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D007891:Leishmania / Q000166:cytology* / Q000254:growth & development* / Q000276:immunology / Q000648:ultrastructure; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008018:Life Cycle Stages / Q000187:drug effects; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology* / Q000648:ultrastructure; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006028:Glycosphingolipids; D006657:Histones; C008290:lipophosphonoglycan; D013755:Tetradecanoylphorbol Acetate