NETosis in Parasitic Infections: A Puzzle That Remains Unsolved

Abstract

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.

Neutrophil Extracellular Traps Formation: Effect of Leishmania major promastigotes and salivary gland homogenates of Phlebotomus papatasi in human neutrophil culture

“…It was shown that most microorganisms, like Leishmania parasites induce classical or suicidal NETosis under in vitro conditions. This kind of NETosis starts 2 to 4 hours after exposure and depends on ROS production of NADPH oxidase, besides neutrophil chromatin de-condensation mediated by MPO, NE, and PAD4 [41].…”

“…There is a study indicating that promastigotes of L. amazonensis are capable of inducing both classical and vital NETosis [47]. Early or vital NETosis occurs 5 to 15 up to 30 minutes after stimulation of neutrophils and it is independent of ROS production [41].…”

Immunomodulatory effects of hydatid antigens on mesenchymal stem cells: gene expression alterations and functional consequences

“…Chemokines are known to regulate immune cell recruitment, including monocytes and neutrophils, which are typically the first to be recruited around the parasite ( Legler and Thelen, 2016 ). Neutrophils exhibit anti-parasitic effects through phagocytosis, degranulation, and the formation of neutrophil extracellular trapping networks (NETs) ( Díaz-Godínez and Carrero, 2019 ; Omar and Abdelal, 2023 ). Similarly, macrophages may hinder parasite survival through phagocytosis, NO production, and pro-inflammatory cytokine release ( Silva-Álvarez et al, 2016 ; Lin et al, 2021 ).…”

Exploration of altered miRNA expression and function in MSC-derived extracellular vesicles in response to hydatid antigen stimulation

“…Previous studies have indicated the physiological significance of chemokine expression in MSCs, as they recruit various immune cells ( Fernández-Francos et al, 2021 ). Neutrophils and macrophages, the first cells recruited around the worm, may exert antiparasitic effects through phagocytosis, degranulation, or the formation of neutrophil extracellular trapping networks (NETs) ( Omar and Abdelal, 2023 ). Alterations in chemokine expression in MSCs may have multiple biological effects and are closely related to lesion development ( Yao et al, 2021 ).…”