Figure 1.

Induction, antiviral effect, and viral evasion of NETs. (1) Formation of NETs is induced directly by virions (red) through PRRs (blue) expressed by neutrophils on the surface (TLR4, β2 integrins) or in endosomes (TLR7, 8) or indirectly by proinflammatory mediators (e.g., IL-8), which are released from virus-infected cells (orange). In addition, viral activation of the platelet/neutrophil axis can trigger NETosis (green). As a consequence, granules fuse with the nucleus, which subsequently loses its characteristic lobulated shape and ruptures. Finally, neutrophils rupture releasing sticky strings of NETs. (2) NETs have antiviral effects by immobilizing or inactivating free virions, thereby preventing viral spread. NETs also potentiate the release of type I interferon by pDC (not shown), thus increasing the resistance of local cells to further infection. (3) Digestion of the DNA backbone by DNases releases trapped virions. These virions, if not already inactivated, opsonized, or degraded, can attempt to infect further cells. Moreover, viruses can interfere with NETosis by inducing cellular IL-10 or by expressing viral IL-10 homologs (not shown).