Interferon lambda 4 is a gut antimicrobial protein

• 成果类型: Article
• 署名作者: Xiao, Xun; Wang, Jinting; Ma, Jun; Peng, Xuan; Wu, Shengqiang; Chen, Xiaolei; Lu, Hao; Tan, Chen; Fang, Liurong; Xiao, Shaobo
• 署名单位: Huazhong Agricultural University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10428
• DOI: 10.1073/pnas.2409684121
• 发表日期: 2024-10-29
• 关键词: stimulated gene-expression; hepatitis-c; lectin; ifnl4; microbiota; clearance; host; association; receptor; bacteria

摘要

To withstand complex microbial challenges, the mammalian gut largely depends on the secretion of diverse antimicrobial proteins. Type III interferons (IFN lambda s) are ordinarily considered inducible antiviral cytokines involved in intestinal immunity. Unlike other IFN lambda s, we found that newly identified IFN lambda 4 is an intestinal antibacterial protein. Large amounts of natural IFN lambda 4 are present in the secretory layer of the intestinal tracts of healthy piglets, which suggests that IFN lambda 4 is in direct physiological contact with microbial pathogens. We also identified two biochemical functions of mammalian IFN lambda 4, the induction of bacterial agglutination and direct microbial killing, which are not functions of the other IFN lambda s. Further mechanistic investigations revealed that after binding to the carbohydrate fraction of lipopolysaccharide, mammalian IFN lambda 4 self- assembles into bacteria- surrounding nanoparticles that agglutinate bacteria, and that its unique cationic amphiphilic molecular structure facilitates the destruction of bacterial membranes. Our data reveal features of IFN lambda 4 distinct from those of previously reported IFN lambda s and suggest that noncanonical IFN lambda 4 is deeply involved in intestinal immunity, beyond simply cytokine signaling.