Investigating and harnessing the immunoregulatory function of interferons in viral-induced immunopathology

In response to viral infections, immune activation and inflammation must be tightly regulated as too little will impair clearance of an infection, however excessive immune activation can cause irreparable tissue damage and hinder disease tolerance. In the absence of a suitable vaccine, we must be able to effectively treat severe infections, however, our ability to treat viral-induced immunopathology remains poor. Key to regulating our damaging immune responses to all viral infections are our type I and III interferon responses. Attempts to harness type I interferons in the past have been severely limited by the timeliness required for effective type I interferon therapy. In contrast, while the immunoregulatory type III IFNs are poorly defined, growing evidence suggests their high flexibility as a therapeutic avenue, and their potent ability to suppress unwanted immune responses. Both Ebola virus outbreaks and the COVID-19 pandemic have shown that the ability to produce potent interferon response correlates with improved viral clearance and reduced inflammation and disease severity, and demographics more likely to experience severe infections, such as the elderly, have also been demonstrated to elicit a weaker interferon response during infection. Thus, the potential for interferons to be harnessed as a therapeutic due to their immunoregulatory capacities remains highly promising, yet unexploited. In this project, we will be investigating the mechanisms through how type III interferons are able to suppress viral-induced immunopathology and assess how they can be used safely in a therapeutic capacity. We will also investigate the role interferons may play in determining disease susceptibility in aging populations. By understanding the full type III interferons play in regulating disease tolerance, can develop novel therapeutics, that would be applicable to any viral infection, and would prepare us for any current and future epidemic.