Cytonemes Versus Neutrophil Extracellular Traps in the Fight of Neutrophils with Microbes

Abstract

Neutrophils can phagocytose microorganisms and destroy them intracellularly using special bactericides located in intracellular granules. Recent evidence suggests that neutrophils can catch and kill pathogens extracellularly using the same bactericidal agents. For this, live neutrophils create a cytoneme network, and dead neutrophils provide chromatin and proteins to form neutrophil extracellular traps (NETs). Cytonemes are filamentous tubulovesicular secretory protrusions of living neutrophils with intact nuclei. Granular bactericides are localized in membrane vesicles and tubules of which cytonemes are composed. NETs are strands of decondensed DNA associated with histones released by died neutrophils. In NETs, bactericidal neutrophilic agents are adsorbed onto DNA strands and are not covered with a membrane. Cytonemes and NETs occupy different places in protecting the body against infections. Cytonemes can develop within a few minutes at the site of infection through the action of nitric oxide or actin-depolymerizing alkaloids of invading microbes. The formation of NET in vitro occurs due to chromatin decondensation resulting from prolonged activation of neutrophils with PMA (phorbol 12-myristate 13-acetate) or other stimuli, or in vivo due to citrullination of histones with peptidylarginine deiminase 4. In addition to antibacterial activity, cytonemes are involved in cell adhesion and communications. NETs play a role in autoimmunity and thrombosis.

Neutrophil Adhesion and the Release of the Free Amino Acid Hydroxylysine

“…Depolymerization of actin blocks the separation of membrane vesicles from the plasmalemma and from each other. As a result, the secretory process leaves the cell in the form of filamentous cytonemes [ 51 , 52 , 53 , 54 , 55 ].…”

Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights

“…After encountering micro-organisms, neutrophils destroy them intracellularly as well as extracellularly: in their fight with microbes, dead neutrophils provide chromatin and proteins to form NETs and, live neutrophils create a cytoneme network ( 68 ).…”

Membrane nanotubes are ancient machinery for cell-to-cell communication and transport. Their interference with the immune system

“…This complex mechanism can thus eliminate various bacteria by trapping and killing them in a relatively small volume around the neutrophils with high efficiency. Notably, NETs and cytonemes can also be regarded as “double edge sword”, since they may also play some negative roles, as well, for example, in the process of thrombosis and autoimmune diseases (Galkina et al 2020 ).…”

“…A recently increasing interest in neutrophil activities in the immune response also appeared in the nanotube research, together with a special, neutrophil-related microbe-killing mechanism, the neutrophil extracellular trap (NET). During the fight of neutrophils against microorganisms, these two mechanisms seem to work hand-in-hand (Galkina et al 2020(Galkina et al , 2013. In this battle, the live and dead/dying neutrophils seem to collaborate enjoying help from neutrophilderived microvesicles, as well (Timár et al 2013).…”