Neutrophil dynamics in viral infections: drivers of inflammation and targets for pro-resolving therapies

BACKGROUND: Neutrophils are essential components of host defense, traditionally recognized for their well-described antimicrobial functions in bacterial infections. Far from being merely short-lived and functionally limited, emerging evidence demonstrates that neutrophils are also key players in viral infections. Through mechanisms such as degranulation and formation of NETs, neutrophils play an important role in virus-induced inflammation and pathogenesis. However, their persistence and hyperactivated states also contribute to tissue damage and failed resolution of acute inflammation. SUMMARY: Here, we summarize recent data regarding the role of neutrophils in respiratory and arboviral infections, from clinical evidence to mechanistic insights available from the last ten years. Finally, we discuss emerging therapeutic strategies that target neutrophil fate and function to promote the resolution of inflammation. KEY MESSAGES: Overall, although well characterized in some viral infections, for a few other viral diseases the role of neutrophils remains elusive. We highlight the importance of modulating neutrophils death in a timely and non-inflammatory manner, as some viruses influence apoptosis for their own benefit, favoring viral replication. For those infections, and also due to non-resolving inflammation provoked by these viruses, pro-resolving mediators certainly display a beneficial effect. Rather than broadly suppressing antiviral immunity, pro-resolving approaches aimed at recalibrating neutrophil activation, lifespan, and clearance may represent a promising and safer avenue for the treatment of viral diseases characterized by excessive and non-resolving inflammation.