title: The C-Type Lectin Receptor SIGNR3 Binds to Fungi Present in Commensal Microbiota and Influences Immune Regulation in Experimental Colitis.
abstract: Inflammatory bowel disease is a condition of acute and chronic inflammation of the gut. An important factor contributing to pathogenesis is a dysregulated mucosal immunity against commensal bacteria and fungi. Host pattern-recognition receptors (PRRs) sense commensals in the gut and are involved in maintaining the balance between controlled responses to pathogens and overwhelming innate immune activation. C-type lectin receptors (CLRs) are PRRs recognizing glycan structures on pathogens and self-antigens. Here we examined the role of the murine CLR specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related 3 (SIGNR3) in the recognition of commensals and its involvement in intestinal immunity. SIGNR3 is the closest murine homolog of the human dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) receptor recognizing similar carbohydrate ligands such as terminal fucose or high-mannose glycans. We discovered that SIGNR3 recognizes fungi present in the commensal microbiota. To analyze whether this interaction impacts the intestinal immunity against microbiota, the dextran sulfate sodium-induced colitis model was employed. SIGNR3(-/-) mice exhibited an increased weight loss associated with more severe colitis symptoms compared to wild-type control mice. The increased inflammation in SIGNR3(-/-) mice was accompanied by a higher level of TNF-α in colon. Our findings demonstrate for the first time that SIGNR3 recognizes intestinal fungi and has an immune regulatory role in colitis.
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces , Potsdam , Germany ; Department of Biology, Chemistry and Pharmacy, Institute of Chemistry and Biochemistry, Freie Universität Berlin , Berlin , Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Eriksson
authors.forename: Timo
authors.initials: T
authors.lastname: Johannssen
authors.forename: Dorthe
authors.initials: D
authors.lastname: von Smolinski
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
authors.forename: Bernd
authors.initials: B
authors.lastname: Lepenies
keywords: C-type lectin receptor; SIGNR3; carbohydrate recognition; colitis; fungi; host innate immunity; microbiota