Laminaran potentiates cGAS-STING signaling to enhance antiviral responses

Cyclic GMP–AMP synthase (cGAS)-Stimulator of interferon genes (STING) signaling pathway, an essential element in the innate antiviral immune responses, has emerged as a key component of innate immune system to modulate type I IFNs production and response by recognizing both exogenous and endogenous DNA. Although some cGAS-STING signaling small molecule agonists have been developed, there are few natural polysaccharides reported to activate cGAS-STING signaling for the treatment of infectious diseases. Here, we reported that Laminaran, a low molecular weight β-glucan storage polysaccharide present in brown algae, potentiates cGAS-STING signaling to promote type I IFNs production and antiviral response. Laminaran enhanced cGAS-STING signaling mediated type I IFNs production and response both in human and murine cells upon HSV-1 infection or DNA mimics stimulation. Importantly, we found that Laminaran markedly inhibited Herpes simplex virus-1 (HSV-1) induced death and inflammatory responses and increased the induction of type I IFNs in C57BL/6J mice. Mechanistically, we found Laminaran inhibited autophagy and suppressed STING autophagic degradation to positively regulate cGAS-STING signaling response. Taken together, we uncovered the function of Laminaran in DNA triggered innate immunity by enhancing cGAS-STING signaling response. Laminaran might be a potential therapeutic candidate for viral infectious diseases.