<i>Leishmania donovani</i> Promastigotes Evade the Antimicrobial Activity of Neutrophil Extracellular Traps

Gabriel, Christelle; McMaster, W. Robert; Girard, Denis; Descoteaux, Albert

doi:10.4049/jimmunol.1000893

Cited by 168 publications

(141 citation statements)

References 52 publications

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“…This finding was further corroborated by Gabriel and colleagues (13), who demonstrated that L. donovani also induces NET formation. In addition, upon interaction with neutrophils, promastigotes of Leishmania infantum activate NETosis in a time-and dose-dependent manner ( Fig.…”

Section: Leishmania Infantum Promastigotes Induce the Release Of Neutsupporting

confidence: 70%

“…Promastigotes of Leishmania infantum induced NETosis in a dose-and time-dependent manner. Furthermore, NET induction seems to be conserved in different species of Leishmania (12,13). In addition, as previously reported, human neutrophil donors differed in the magnitude of their NET response to different stimuli (3).…”

Section: Discussionmentioning

confidence: 52%

“…Additionally, it was demonstrated that while Leishmania donovani triggers NET formation, it evades NET-mediated killing due to its lipophosphoglycan (LPG) (13). Here, we demonstrate that promastigotes of Leishmania infantum induce NET release in a doseand time-dependent manner and evade NET-mediated killing through their 3=NT/NU activity.…”

Section: Discussionmentioning

confidence: 69%

“…To date, bacteria, fungi, viruses, and protozoan parasites have been shown to induce NETosis in neutrophils (2,4,12,13,(40)(41)(42)(43). Among parasites, Leishmania spp., Eimeria bovis, and Toxoplasma gondii were reported to activate NETosis (12, 13, 40, 41).…”

Section: Discussionmentioning

confidence: 99%

“…Gabriel and colleagues (13) demonstrated that Leishmania donovani promastigotes evade NET toxicity due to the presence of LPG, as wild-type parasites had greater survival than LPG knockout promastigotes. Interestingly, the addition of DNase to the culture rescued LPG knockouts but not wild-type parasites from death.…”

Section: Discussionmentioning

confidence: 99%

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3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

et al. 2014

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Leishmaniasis is a widespread neglected tropical disease caused by parasites of the Leishmania genus. These parasites express the enzyme 3=-nucleotidase/nuclease (3=NT/NU), which has been described to be involved in parasite nutrition and infection. Bacteria that express nucleases escape the toxic effects of neutrophil extracellular traps (NETs). Hence, we investigated the role of 3=NT/NU in Leishmania survival of NET-mediated killing. Promastigotes of Leishmania infantum were cultured in high-phosphate (HP) or low-phosphate (LP) medium to modulate nuclease activity. We compared the survival of the two different groups of Leishmania during interaction with human neutrophils, assessing the role of neutrophil extracellular traps. As previously reported, we detected higher nuclease activity in parasites cultured in LP medium. Both LP and HP promastigotes were capable of inducing the release of neutrophil extracellular traps from human neutrophils in a dose-and time-dependent manner. LP parasites had 2.4 times more survival than HP promastigotes. NET disruption was prevented by the treatment of the parasites with ammonium tetrathiomolybdate (TTM), a 3=NT/NU inhibitor. Inhibition of 3=NT/NU by 3=-AMP, 5=-GMP, or TTM decreased promastigote survival upon interaction with neutrophils. Our results show that Leishmania infantum induces NET release and that promastigotes can escape NET-mediated killing by 3=-nucleotidase/nuclease activity, thus ascribing a new function to this enzyme. N eutrophils are short-lived cells and the most abundant leukocytes in the blood circulation; they constitute one of the first lines of defense against invading microorganisms (1). These granulocytes can kill microorganisms by phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are weblike structures composed of chromatin, granules, and cytoplasmic proteins that are extruded when neutrophils undergo NETosis, a unique cell death mechanism (2-5). However, recent work challenges NETosis as a cell death mechanism because live neutrophils were detected after NET extrusion in in vivo studies (6). NETs function by killing and containing pathogens, thereby preventing the pathogen's dissemination through the organism. In addition, some studies have indicated that NETs play a role in autoimmune diseases (7-10).A diverse group of stimuli has been described as activating NETosis (5, 11). Among the parasites, Leishmania promastigotes were demonstrated to activate release of NETs (12, 13). Leishmania amazonensis promastigotes interact intimately with NETs and are killed by web-associated histones (12). However, although promastigotes of Leishmania donovani trigger NET release, these parasites escape the toxicity of NETs (13). Groups of microorganisms have evolved different mechanisms of escaping the toxic effects of NETs. Streptococcus pneumoniae, group A Streptococcus, Streptococcus agalactiae, Staphylococcus aureus, and Vibrio cholerae express endonucleases that efficiently degrade DNA filaments from NETs, allowing these bacteria...

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Section: Leishmania Infantum Promastigotes Induce the Release Of Neutsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

et al. 2014

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Interaction ofLeishmaniaParasites with Host Cells and its Functional Consequences

Schurigt¹,

Masic²,

Moll³

2013

Trypanosomatid Diseases

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Untangling “NETosis” from NETs

et al. 2019

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Neutrophil extracellular trap (NET) formation is a cellular function of neutrophils thatfacilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form NETs, neutrophils release a DNA scaffold consisting of mitochondrial DNA binding granule proteins. This process does not depend on cell death, but requires glycolytic ATP production for rearrangements in the microtubule network and F-actin. Such cytoskeletal rearrangements are essential for both mitochondrial DNA release and degranulation. However, the formation of NETs has also been described as a distinct form of programed, necrotic cell death, a process designated "NETosis." Necrotic cell death of neutrophils is associated with the permeabilization of both plasma and nuclear membranes resulting in a kind of extracellular cloud of nuclear DNA. The molecular mechanisms eliciting necrotic neutrophil death have been investigated and appear to be different from those responsible for NET formation following mitochondrial DNA release. Here, we discriminate between the mechanisms responsible for the release of mitochondrial versus nuclear DNA and address their respective functions. Our aim is to clarify existing differences of opinion in the fields of NET formation and neutrophil death.

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Leishmania donovani Promastigotes Evade the Antimicrobial Activity of Neutrophil Extracellular Traps

Cited by 168 publications

References 52 publications

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

3′-Nucleotidase/Nuclease Activity Allows Leishmania Parasites To Escape Killing by Neutrophil Extracellular Traps

Interaction ofLeishmaniaParasites with Host Cells and its Functional Consequences

Untangling “NETosis” from NETs

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