3-Fucosyllactose-mediated modulation of immune response against virus infection

• Published in: International journal of antimicrobial agents 2024-07, Vol.64 (1), p.107187, Article 107187
• Main Authors: Moon, Seokoh, Lee, Ki Wook, Park, Myungseo, Moon, Jeonghui, Park, Sang Hee, Kim, Soomin, Hwang, Jaehyeon, Yoon, Jong-Won, Jeon, Seon-Min, Kim, Jun-Seob, Jeon, Young-Jun, Kweon, Dae-Hyuk
• Format: Article
• Language: English
• Subjects: 3-fucosyllactose; breast milk; cell culture; dietary supplements; Human milk oligosaccharides; immune response; immunomodulators; inflammation; influenza; Influenza virus; Interferon receptors; interferon-gamma; leukocytes; lungs; mice; nitric oxide; oligosaccharides; SARS-CoV-2; sequence analysis; Severe acute respiratory syndrome coronavirus 2; viruses
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2024.107187

•Administration of 3-fucosylactose increased leukocyte migration and decreased lethality and viral titres in mice infected with influenza virus.•Prolonged treatment of 3-fucosylactose induced antiviral effects in various types of cells against a broad spectrum of viruses, including influenza viruses and pseudo-coronavirus.•In the resting state, 3-fucosyllactose upregulated interferon receptors while downregulating interferon-stimulated genes leading to potential enhancement of the antiviral response.•During viral infections, high levels of interferon receptors induced by 3-fucosyllactose promoted antiviral innate immunities, including nitric oxide production, expression of ISGs, and innate immune cells-related genes that inhibit viral infections. Viral pathogens, particularly influenza and SARS-CoV-2, pose a significant global health challenge. Given the immunomodulatory properties of human milk oligosaccharides, in particular 2′-fucosyllactose and 3-fucosyllactose (3-FL), we investigated their dietary supplementation effects on antiviral responses in mouse models. This study revealed distinct immune modulations induced by 3-FL. RNA-sequencing data showed that 3-FL increased the expression of interferon receptors, such as Interferon Alpha and Beta Receptor (IFNAR) and Interferon Gamma Receptor (IFNGR), while simultaneously downregulating interferons and interferon-stimulated genes, an effect not observed with 2′-fucosyllactose supplementation. Such modulation enhanced antiviral responses in both cell culture and animal models while attenuating pre-emptive inflammatory responses. Nitric oxide concentrations in 3-FL-supplemented A549 cells and mouse lung tissues were elevated exclusively upon infection, reaching 5.8- and 1.9-fold increases over control groups, respectively. In addition, 3-FL promoted leukocyte infiltration into the site of infection upon viral challenge. 3-FL supplementation provided protective efficacy against lethal influenza challenge in mice. The demonstrated antiviral efficacy spanned multiple influenza strains and extended to SARS-CoV-2. In conclusion, 3-FL is a unique immunomodulator that helps protect the host from viral infection while suppressing inflammation prior to infection. [Display omitted]