Gene Set Enrichment Analysis Reveals That Fucoidan Induces Type I IFN Pathways in BMDC

Abstract

Abstract Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has been proposed to effectively treat and prevent various viral infections. However, the mechanisms behind its antiviral activity are not completely understood. We investigate here the global transcriptional changes in bone marrow-derived dendritic cells (BMDCs) using RNA-Seq technology. Through both analysis of differentially expressed genes (DEG) and gene set enrichment analysis (GSEA), we found that fucoidan-treated BMDCs were enriched in virus-specific response pathways, including that of SARS-CoV-2, as well as pathways associated with nucleic acid-sensing receptors (RLR, TLR, NLR, STING), and type I interferon (IFN) production. We show that these transcriptome changes are driven by well-known regulators of the inflammatory response against viruses, including IRF, NF-κB, and STAT family transcription factors. Furthermore, 435 of the 950 upregulated DEGs are classified as type I IFN-stimulated genes (ISGs). Flow cytometric analysis additionally showed that fucoidan increased MHCII, CD80, and CD40 surface markers in BMDCs, indicative of greater antigen presentation and co-stimulation functionality. Our current study suggests that fucoidan transcriptionally activates PRR signaling, type I IFN production and signaling, ISGs production, and DC maturation, highlighting a potential mechanism of fucoidan-induced antiviral activity. 이 연구는 충남대학교 연구비와 교육부 조성 한국연구재단(NRF-2019R1I1A3A01060331 to J.K.) 또한, 과학기술정보통신부가 지원하는 한국연구재단(NRF)을 통한 브레인풀 프로그램(NRF-2020H1D3A2A02048437, J.G.K.)과 과학기술부(NRF-2021M3H9A1030267, S.Y.K.)의 지원으로 진행됐다.