Lypd8 inhibits attachment of pathogenic bacteria to colonic epithelia

• Published in: Mucosal immunology Vol. 13; no. 1; pp. 75 - 85
• Main Authors: Okumura, Ryu, Kodama, Toshio, Hsu, Chiao-Ching, Sahlgren, Benjamin Heller, Hamano, Shota, Kurakawa, Takashi, Iida, Tetsuya, Takeda, Kiyoshi
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 2020; Elsevier Limited
• Subjects: Adhesins, Bacterial - metabolism; Aged; Allergology; Animals; Antibodies; Bacteria; Bacterial Adhesion; Biomedical and Life Sciences; Biomedicine; Citrobacter rodentium - physiology; Colitis; Colon; Colon - pathology; Colonization; Enterobacteriaceae Infections - immunology; Enterobacteriaceae Infections - metabolism; Enterocytes; Epithelial cells; Gastroenterology; Glycosylphosphatidylinositol; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Helper cells; Homeostasis; Humans; Immunity, Innate; Immunology; Inflammatory bowel disease; Innate immunity; Intestinal Mucosa - microbiology; Intestinal Mucosa - physiology; Intestine; Intimin; Lamina propria; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucosa; Mucous Membrane - immunology; Mucous Membrane - microbiology; Neutrophil Activation; Pathogens; Th17 Cells - immunology; Translocated intimin receptor
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-019-0219-4

Mucosal barriers segregate commensal microbes from the intestinal epithelia to maintain gut homeostasis. Ly6/Plaur domain-containing 8 (Lypd8), a highly glycosylated glycosylphosphatidylinositol-anchored protein selectively expressed on colonic enterocytes, promotes this segregation by inhibiting bacterial invasion of the inner mucus layer and colonic epithelia. However, it remains unclear whether Lypd8 prevents infection with enteric bacterial pathogens. Here, we demonstrate that Lypd8 strongly contributes to early-phase defense against
Citrobacter rodentium
, which causes colitis by inducing attachment and effacement (A/E) lesions on colonic epithelia. Lypd8 inhibits
C. rodentium
attachment to intestinal epithelial cells by binding to intimin, thereby suppressing the interaction between intimin and translocated intimin receptor. Lypd8 deficiency leads to rapid
C. rodentium
colonization in the colon, resulting in severe colitis with Th17-cell and neutrophil expansion in the lamina propria. This study identifies a novel function for Lypd8 against A/E bacteria and highlights the role of enterocytes as crucial players in innate immunity for protection against enteric bacterial pathogens.