The protective and pathogenic roles of IL-17 in viral infections: friend or foe?

Abstract

Viral infections cause substantial human morbidity and mortality, and are a significant health burden worldwide. Following a viral infection, the host may initiate complex antiviral immune responses to antagonize viral invasion and replication. However, proinflammatory antiviral immune responses pose a great threat to the host if not properly held in check. Interleukin (IL)-17 is a pleiotropic cytokine participating in a variety of physiological and pathophysiological conditions, including tissue integrity maintenance, cancer progression, autoimmune disease development and, more intriguingly, infectious diseases. Abundant evidence suggests that while IL-17 plays a crucial role in enhancing effective antiviral immune responses, it may also promote and exacerbate virus-induced illnesses. Accumulated experimental and clinical evidence has broadened our understanding of the seemingly paradoxical role of IL-17 in viral infections and suggests that IL-17-targeted immunotherapy may be a promising therapeutic option. Herein, we summarize current knowledge regarding the protective and pathogenic roles of IL-17 in viral infections, with emphasis on underlying mechanisms. The various and critical roles of IL-17 in viral infections necessitate the development of therapeutic strategies that are uniquely tailored to both the infectious agent and the infection environment.

The potential role of Th17 immune responses in coronavirus immunopathology and vaccine-induced immune enhancement

“…Despite these concerns, notwithstanding the fact that COVID-19 involves severe pulmonary dysfunction, there remains the unknown contribution of cytokine storm, enhanced Th17 responses, or pulmonary eosinophilia to end-stage mortality (28). Indeed, evidence increasingly suggests that severe morbidity and mortality as seen during COVID-19 may have far more to do with heart dysfunction than pulmonary failure (29,30).…”

Should patients stop their biologic treatment during the COVID-19 pandemic

“…For patients infected, evidence is mixed on the role of Il-17 in the immune response to viruses. Il-17 may have a paradoxical role in both enhancing antiviral immune response and exacerbating viral illness depending on the virus (11). However, it is hypothesized that agents blocking this pathway could have the potential to improve COVID-19's aberrant immune response and acute respiratory distress syndrome-related mortality (12).…”

Identification and Regulation of Interleukin-17 (IL-17) Family Ligands in the Teleost Fish European Sea Bass

“…Viruses may simultaneously activate multiple IL-17-producing cell subsets that differ in several key biological activities [33]. Strikingly, in mammals, IL-17 ligands have a dual positive and negative protective role against viral infections [36]. However, the inflammatory processes triggered by viral infections in fish are less known.…”

“…During viral infection, the high production of IL-17A, IL-17F, and IL-22 has been directly related with inflamed tissues [38]. The role of IL-17 in mammals has been related to proinflammatory properties that make IL-17 an essential mediator of inflammation and immunopathology [36]. This would imply a proinflammatory state due to viral infection.…”