Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps

被引：447

作者：

Guimaraes-Costa, Anderson B. ^{[1
]}

Nascimento, Michelle T. C. ^{[1
]}

Froment, Giselle S. ^{[1
]}

Soares, Rodrigo P. P. ^{[2
]}

Morgado, Fernanda N. ^{[3
]}

Conceicao-Silva, Fatima ^{[3
]}

Saraiva, Elvira M. ^{[1
]}

机构：

[1] Univ Fed Rio de Janeiro, Dept Imunol, Inst Microbiol Prof Paulo de Goes, BR-21941902 Rio De Janeiro, Brazil

[2] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Entomol Med, BR-30190002 Belo Horizonte, MG, Brazil

[3] Fundacao Oswaldo Cruz, Lab Imunoparasitol, BR-21045900 Rio De Janeiro, Brazil

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 16期

关键词：

histone; protozoa; trypanosomatid; PARASITES; LIPOPHOSPHOGLYCAN; GRANULOCYTES; DONOVANI; PREECLAMPSIA; MACROPHAGES; MICROBES; IMMUNITY; NETS;

D O I：

10.1073/pnas.0900226106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：6748 / 6753

页数：6

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