Hookworm infections: Reappraising the evidence for a role of neutrophils in light of NETosis

Doolan, Rory; Bouchery, Tiffany

doi:10.1111/pim.12911

Cited by 6 publications

(5 citation statements)

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“…Eosinophils as well as neutrophils formed extracellular traps (as reported for parasites in the pleural cavity; Ehrens et al, 2021a ), and each cell type contributed key toxic molecules (major basic protein and myeloperoxidase, respectively), in a manner enhanced by specific antibody ( Ehrens et al, 2021b ). The demonstration of trap formation at the physiological site of infection builds on earlier work showing NET formation against the human parasite Strongyloides stercoralis in vitro and following intraperitoneal injection into mice ( Bonne-Année et al, 2014 ), and fits within a recognition of the broader roles of neutrophils in immunity to helminths ( Chen et al, 2014 ; Doolan and Bouchery, 2022 ). This study epitomizes the key points of immunity to helminths, in which each species is targeted by a bespoke combination of innate effector cell populations that are dependent on adaptive immune activation and the specific tissue site of invasion, ultimately deploying multiple molecular strategies to eliminate the parasite ( Fig.…”

Section: Immunity In the Skin: Tricks And Trapssupporting

confidence: 56%

Targeting helminths: The expanding world of type 2 immune effector mechanisms

Maizels,

Gause

2023

Journal of Experimental Medicine

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Section: Immunity In the Skin: Tricks And Trapssupporting

confidence: 56%

Targeting helminths: The expanding world of type 2 immune effector mechanisms

Maizels,

Gause

2023

Journal of Experimental Medicine

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“…Meanwhile, numerous reports have studied the crucial role of NETosis against inv sive protozoan [2,32,43,44,58,[63][64][65][66] and helminth parasites [2,6,40,67,68]. However, s far, there is only one report on C. parvum-induced suicidal NETosis in the literature [2 We have shown that C. parvum sporozoite and oocyst-mediated suicidal NETosis occu by establishing co-localization of nuclear H1A, H2A/B, H3-4, and NE in DNA-rich NE complexes produced by C. parvum.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, numerous reports have studied the crucial role of NETosis against invasive protozoan [2,32,43,44,58,[63][64][65][66] and helminth parasites [2,6,40,67,68]. However, so far, there is only one report on C. parvum-induced suicidal NETosis in the literature [2].…”

Section: Discussionmentioning

confidence: 99%

ATP Purinergic Receptor P2X1-Dependent Suicidal NETosis Induced by Cryptosporidium parvum under Physioxia Conditions

Hasheminasab

Conejeros

Velásquez

et al. 2022

Biology

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Cryptosporidiosis is a zoonotic intestinal disease that affects humans, wildlife, and neonatal cattle, caused by Cryptosporidium parvum. Neutrophil extracellular traps (NETs), also known as suicidal NETosis, are a powerful and ancient innate effector mechanism by which polymorphonuclear neutrophils (PMN) battle parasitic organisms like protozoa and helminths. Here, C. parvum oocysts and live sporozoites were utilized to examine suicidal NETosis in exposed bovine PMN beneath both 5% O2 (physiological conditions within small intestinal tract) and 21% O2 (normal hyperoxic conditions in research facilities). Both sporozoites and oocysts induced suicidal NETosis in exposed PMN under physioxia (5% O2) and hyperoxia (21% O2). Besides, C. parvum-induced suicidal NETosis was affirmed by total break of PMN, co-localization of extracellular DNA decorated with pan-histones (H1A, H2A/H2B, H3, H4) and neutrophil elastase (NE) by means of confocal- and immunofluorescence microscopy investigations. C. parvum-triggered NETs entrapped sporozoites and impeded sporozoite egress from oocysts covered by released NETs, according to scanning electron microscopy (SEM) examination. Live cell 3D-holotomographic microscopy analysis visualized early parasite-induced PMN morphological changes, such as the formation of membrane protrusions towards C. parvum while undergoing NETosis. Significant reduction of C. parvum-induced suicidal NETosis was measured after PMN treatments with purinergic receptor P2X1 inhibitor NF449, under both oxygen circumstances, this receptor was found to play a critical role in the induction of NETs, indicating its importance. Similarly, inhibition of PMN glycolysis via 2-deoxy glucose treatments resulted in a reduction of C. parvum-triggered suicidal NETosis but not significantly. Extracellular acidification rates (ECAR) and oxygen consumption rates (OCR) were not increased in C. parvum-exposed cells, according to measurements of PMN energetic state. Treatments with inhibitors of plasma membrane monocarboxylate transporters (MCTs) of lactate failed to significantly reduce C. parvum-mediated NET extrusion. Concerning Notch signaling, no significant reduction was detected after PMN treatments with two specific Notch inhibitors, i.e., DAPT and compound E. Overall, we here describe for the first time the pivotal role of ATP purinergic receptor P2X1 in C. parvum-mediated suicidal NETosis under physioxia (5% O2) and its anti-cryptosporidial properties.

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“…The DNA webs exhibited both trapping and direct killing properties against the infective (L3) larvae by inducing cuticle damage (Figure 2C), resulting in increased permeability to the DNA binding dye Sytox-Green. Temperature activation enhanced the larval secretion of the DNase-II enzyme, which was capable of degrading the NET strands to escape trapping and cuticle damage [65].…”

Section: Direct Killing (Larvicidal) Effectsmentioning

confidence: 99%

NETosis in Parasitic Infections: A Puzzle That Remains Unsolved

Omar

Abdelal²

2023

IJMS

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Neutrophils are the key players in the innate immune system, being weaponized with numerous strategies to eliminate pathogens. The production of extracellular traps is one of the effector mechanisms operated by neutrophils in a process called NETosis. Neutrophil extracellular traps (NETs) are complex webs of extracellular DNA studded with histones and cytoplasmic granular proteins. Since their first description in 2004, NETs have been widely investigated in different infectious processes. Bacteria, viruses, and fungi have been shown to induce the generation of NETs. Knowledge is only beginning to emerge about the participation of DNA webs in the host’s battle against parasitic infections. Referring to helminthic infections, we ought to look beyond the scope of confining the roles of NETs solely to parasitic ensnarement or immobilization. Hence, this review provides detailed insights into the less-explored activities of NETs against invading helminths. In addition, most of the studies that have addressed the implications of NETs in protozoan infections have chiefly focused on their protective side, either through trapping or killing. Challenging this belief, we propose several limitations regarding protozoan-NETs interaction. One of many is the duality in the functional responses of NETs, in which both the positive and pathological aspects seem to be closely intertwined.

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Hookworm infections: Reappraising the evidence for a role of neutrophils in light of NETosis

Cited by 6 publications

References 93 publications

Targeting helminths: The expanding world of type 2 immune effector mechanisms

Targeting helminths: The expanding world of type 2 immune effector mechanisms

ATP Purinergic Receptor P2X1-Dependent Suicidal NETosis Induced by Cryptosporidium parvum under Physioxia Conditions

NETosis in Parasitic Infections: A Puzzle That Remains Unsolved

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