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Background: Interferon epsilon (IFN-ε) is a type I IFN that plays a critical role in the host immune response against pathogens. Despite having demonstrated antiviral activity in macrophages and mucosal tissues such as the female reproductive tract and the constitutive expression in mucosal tissues such as the lung, the relevance of IFN-ε against respiratory viral infections remains elusive. Results: We present, for the first time, the expression of IFN-ε in alveolar epithelial cells and primary human bronchial epithelial cells grown in an air–liquid interface (ALI) in response to human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) infection. The molecular characterization of the IFN-ε induction by the viruses indicates that the expression of RIG-I is necessary for an optimal IFN-ε expression. Furthermore, treatment of the airway epithelial cells with rhIFN-ε induced the expression of IFN-stimulated genes (ISGs) and significantly restricted the viral replication of HMPV and RSV. Conclusions: These findings underscore the relevance of IFN-ε against viral infections in the respiratory tract. [ABSTRACT FROM AUTHOR]

Background: Interferon epsilon (IFN-ε) is a type I IFN that plays a critical role in the host immune response against pathogens. Despite having demonstrated antiviral activity in macrophages and mucosal tissues such as the female reproductive tract and the constitutive expression in mucosal tissues such as the lung, the relevance of IFN-ε against respiratory viral infections remains elusive. Results: We present, for the first time, the expression of IFN-ε in alveolar epithelial cells and primary human bronchial epithelial cells grown in an air–liquid interface (ALI) in response to human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) infection. The molecular characterization of the IFN-ε induction by the viruses indicates that the expression of RIG-I is necessary for an optimal IFN-ε expression. Furthermore, treatment of the airway epithelial cells with rhIFN-ε induced the expression of IFN-stimulated genes (ISGs) and significantly restricted the viral replication of HMPV and RSV. Conclusions: These findings underscore the relevance of IFN-ε against viral infections in the respiratory tract.

Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS-CoV-2 response upon infection. To further characterize age-related differences, we studied type I and III interferon (IFN) response in SARS-CoV-2 infected and non-infected individuals of different ages. Specifically, levels of expression of type I (IFN-α, -β, -ε and -ω), type III (IFN-λ1, -λ2 and -λ3) IFNs and of the IFN-stimulated genes, ISG15 and ISG56 were quantified in nasopharyngeal cells from diagnostic swabs. Basal transcription of type I/III IFN genes was highest among children and decreased with age. Among SARS-CoV-2-infected individuals, only IFN-ε and -ω levels were significantly higher in children and young adults whereas ISGs were overexpressed in infected adults. The occurrence of symptoms in children and the need for hospitalization in adults were associated to higher transcription of several IFN genes. Starting from a pre-activated transcription level, the expression of type I and III IFNs was not highly up-regulated in children upon SARS-CoV-2 infection; young adults activated IFNs’ transcription at intermediate levels whereas older adults were characterized by higher ISGs and lower IFN-ε and -ω relative expression levels. Overall, our findings contribute to recognize components of a protective IFN response as a function of age, in the context of SARS-CoV-2 infection.

It has been well-established that type I interferons (IFN-Is) have pleiotropic effects and play an early central role in the control of many acute viral infections. However, their pleiotropic effects are not always beneficial to the host and in fact several reports suggest that the induction of IFN-Is exacerbate disease outcomes against bacterial and chronic viral infections. In this brief review, we probe into this mystery and try to develop answers based on past and recent studies evaluating the roles of IFN-Is in infection and immunity as this is vital for developing effective IFN-Is based therapeutics and vaccines. We also discuss the biological roles of an emerging IFN-I, namely IFN-ε, and discuss its potential use as a mucosal therapeutic and/or vaccine adjuvant. Overall, we anticipate the discussions generated in this review will provide new insights for better exploiting the biological functions of IFN-Is in developing efficacious therapeutics and vaccines in the future.

It has been well-established that type I interferons (IFN-Is) have pleiotropic effects and play an early central role in the control of many acute viral infections. However, their pleiotropic effects are not always beneficial to the host and in fact several reports suggest that the induction of IFN-Is exacerbate disease outcomes against some bacterial and chronic viral infections. In this brief review,we probe into thismystery and try to develop answers based on past and recent studies evaluating the roles of IFN-Is in infection and immunity as this is vital for developing effective IFN-Is based therapeutics and vaccines. We also discuss the biological roles of an emerging IFN-I, namely IFN-ε, and discuss its potential use as a mucosal therapeutic and/or vaccine adjuvant. Overall, we anticipate the discussions generated in this review will provide new insights for better exploiting the biological functions of IFN-Is in developing efficacious therapeutics and vaccines in the future. [ABSTRACT FROM AUTHOR]