Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2021-10, Vol.146, p.155637-155637, Article 155637
• Main Authors: Todorović-Raković, Nataša, Whitfield, Jonathan R.
• Format: Article
• Language: English
• Subjects: Adaptive Immunity - immunology; Antiviral Agents - immunology; Antiviral Agents - therapeutic use; COVID-19 - immunology; COVID-19 - virology; COVID-19 Drug Treatment; Cytokines; Humans; IFNγ; Immune Tolerance - immunology; Immunity, Innate - immunology; Immunomodulation; Immunotolerance; Interferon-gamma - immunology; Interferon-gamma - therapeutic use; Pandemic; Receptors, Interferon - immunology; Review; SARS-CoV-2; SARS-CoV-2 - drug effects; SARS-CoV-2 - immunology; SARS-CoV-2 - physiology; Signal Transduction - immunology
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2021.155637

•IFNγ stands out as a promising endogenous biomarker in various diseases.•IFNγ exemplifies a biomarker with a complex role in virus-host interactions.•It has specific antiviral roles in virus infections including SARS-CoV-2.•Administering IFNγ is a potential therapeutic option against virus infections. Interferons have prominent roles in various pathophysiological conditions, mostly related to inflammation. Interferon-gamma (IFNγ) was, initially discovered as a potent antiviral agent, over 50 years ago, and has recently garnered renewed interest as a promising factor involved in both innate and adaptive immunity. When new disease epidemics appear such as SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus), IAV (Influenza A virus), and in particular the current SARS-CoV-2 pandemic, it is especially timely to review the complexity of immune system responses to viral infections. Here we consider the controversial roles of effectors like IFNγ, discussing its actions in immunomodulation and immunotolerance. We explore the possibility that modulation of IFNγ could be used to influence the course of such infections. Importantly, not only could endogenous expression of IFNγ influence the outcome, there are existing IFNγ therapeutics that can readily be applied in the clinic. However, our understanding of the molecular mechanisms controlled by IFNγ suggests that the exact timing for application of IFNγ-based therapeutics could be crucial: it should be earlier to significantly reduce the viral load and thus decrease the overall severity of the disease.