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.histone ͉ protozoa ͉ trypanosomatid

No abstract

Background: Neutrophil extracellular traps (NETs) are DNA meshes that snare and kill microorganisms, impeding their dissemination.Results: Glucose but not fructose supports NET formation through a metabolic shift toward pentose phosphate pathway (PPP).Conclusion: PPP impairment leads to decreased NET production.Significance: This study provides novel knowledge about the mechanisms of NET induction, opening new avenues of study and intervention.

Phlebotomine Of all these events, the attachment of promastigotes to midgut epithelial cells might be most likely to explain, at least in part, species-related differences in vectorial competence, since it is controlled by molecules which display extensive interspecies polymorphisms (5). Adhesion of Leishmania major promastigotes to midguts of their natural vector, Phlebotomus papatasi, was found to be an inherent property of logarithmic-phase (procyclic) promastigotes controlled by the expression of terminally exposed galactose residues on the lipophosphoglycan (LPG), the major promastigote surface molecule. Among the earliest methods used for species identification was serotyping of spent-medium excreted factor (EF) (8), which is now known to contain a shed form of LPG (9). In all species studied to date, the LPGs comprise linear chains of phosphorylated oligosaccharide repeats which are anchored to the membrane via a glycosylphosphatidylinositol anchor (reviewed in refs. 10 and 11). The phosphoglycan moieties share a common backbone consisting of repeating disaccharide units of where the 3 position of the Gal residue can either be unsubstituted [as in East African isolates of L. donovani (12)