Mechanisms of inflammation-triggered taste loss and its recovery

PROJECT SUMMARY Taste loss can lead to malnutrition, weight loss, and depression. In addition, changes in taste are a symptom of poor health. This cyclical relationship between taste and health highlights the importance of research aimed at understanding taste loss in both health and disease. Research on taste loss will provide new approaches in the prevention, diagnosis, and treatment of disease. It is well-documented that infections and autoimmune conditions are accompanied by changes in chemosensory perception including changes in taste. However, currently we know little about how taste bud regeneration is regulated, and there is no effective treatment for taste loss. Our recent research indicates that inflammation, characterized by induction of inflammatory cytokines and infiltration and activation of immune cells, contributes significantly to taste dysfunction. We hypothesize that inflammation, particularly through the action of the inflammatory cytokine interferon-γ (IFN-γ), contributes to taste loss by inducing cell death and inhibiting taste bud cell renewal, and that resolution of inflammation promotes taste bud regeneration. IFN-γ can be produced by various types of immune and nonimmune cells in response to infections and autoimmunity. Its levels in taste tissues are markedly increased in an autoimmune disease model with taste loss. Yet, whether IFN-γ directly contributes to taste loss has not been determined. In this project, we propose to investigate the role of inflammation, especially IFN-γ, in taste loss using both a transgenic approach and a clinically relevant respiratory viral infection model. We will then use these taste loss models to study the mechanisms of taste bud regeneration. This research will test mechanistic hypotheses of how inflammation and infection cause taste loss, and how taste responses recover. To underscore the importance of research investigating the link between inflammation, disease, and taste loss, a considerable number of COVID-19 patients experience taste dysfunction. Although most cases of taste loss are temporary, including taste loss associated with SARS-CoV-2 infection, long-term taste loss can occur in some patients. Thus, insights from this research will be informative to better understand taste loss in general, as well as taste loss associated with COVID-19.