β-Glucan Induces Training Immunity to Promote Antiviral Activity by Activating TBK1

Abstract

Many studies have shown that β-glucan induces a trained immune phenotype in innate immune cells to defend against bacterial and fungal infections. The specific mechanism involves cellular metabolism and epigenetic reprogramming. However, it is unclear whether β-glucan plays a role in antiviral infection. Therefore, this study investigated the role of trained immunity induced by Candida albicans and β-glucan in antiviral innate immunity. It showed that C. albicans and β-glucan promoted the expression of interferon-β (IFN-β) and interleukin-6 (IL-6) in mouse macrophages triggered by viral infection. In addition, β-glucan pretreatment attenuated the pathological damage induced by the virus in mouse lungs and promoted the expression of IFN-β. Mechanistically, β-glucan could promote the phosphorylation and ubiquitination of TANK Binding Kinase 1 (TBK1), a key protein of the innate immune pathway. These results suggest that β-glucan can promote innate antiviral immunity, and this bioactive material may be a potential therapeutic target for antiviral treatment.

Trained immunity: Target for prophylaxis and therapy

“…The fungal cell wall component b-glucan induces trained immunity by generating longterm functional changes in mononuclear phagocytes via HSPCs activation in the bone marrow 48 and improved resistance to acute infection against various microbial infections such as Leishmania braziliensis 52 Mycobacterium tuberculosis (Mtb), 49 Staphylococcus aureus 53 or Leptospira, 54 and antiviral activity against Vesicular stomatitis virus (VSV) or herpes simplex virus type 1 (HSV-1). 55 Zymosan, a yeast cell wall derivative rich in b-glucan, protects against lethal infections in peritonitis or listeriosis models, 56 whereas another fungal cell wall component with trained immunity properties, chitin, mediates resistance against heterologous Candida albicans systemic infection. 57 Notably, fungal intestinal colonization after rewilding of laboratory mice or oral inoculation conferred long-term protection against bacterial infection pointing out the role of gut microbiota in sustained heterologous protection.…”