2. Academic Validation
  3. Laminaran potentiates cGAS-STING signaling to enhance antiviral responses

Laminaran potentiates cGAS-STING signaling to enhance antiviral responses

  • Int Immunopharmacol. 2025 Feb 6:147:114014. doi: 10.1016/j.intimp.2025.114014.
Lingxiao Xu 1,  Jiao Lyu 2,  Zuocheng Qiu 3,  Qianghui Liu 4,  Huan Hu 5,  Longwei Zhao 6,  Mingyu Pan 7
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, China; Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, China, Nanjing, China.
  • 2 School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
  • 3 Guangdong Provincial Key Laboratory of Speed Capability Research, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
  • 4 Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 5 Department of Biomedical Science, City University of Hong Kong, Kowloon, Hong Kong, China.
  • 6 State Key Laboratory for Macromolecule Drugs and Large-scale Preparation, Department of Pharmacology, Wenzhou Medical University, Wenzhou, China.
  • 7 School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; Department of Biomedical Science, City University of Hong Kong, Kowloon, Hong Kong, China. Electronic address: mingypan@cityu.edu.hk.
PMID: 39793225 DOI: 10.1016/j.intimp.2025.114014
Abstract

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.

Keywords

Antivirus; Autophagy; Innate immunity; Laminaran; STING.

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