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Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2009 Apr 21; Vol. 106 (16), pp. 6748-53. Date of Electronic Publication: 2009 Apr 03. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Animals
Cell Death drug effects
Extracellular Space drug effects
Glycosphingolipids pharmacology
Histones metabolism
Humans
Leishmania immunology
Leishmania ultrastructure
Leishmaniasis, Cutaneous immunology
Leishmaniasis, Cutaneous parasitology
Leishmaniasis, Cutaneous pathology
Neutrophil Activation drug effects
Neutrophils drug effects
Neutrophils ultrastructure
Tetradecanoylphorbol Acetate pharmacology
Extracellular Space immunology
Leishmania cytology
Leishmania growth & development
Life Cycle Stages drug effects
Neutrophils immunology
Neutrophils parasitology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 106
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 19346483
- Full Text :
- https://doi.org/10.1073/pnas.0900226106