Lypd8 inhibits attachment of pathogenic bacteria to colonic epithelia


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.

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We thank T. Kondo and Y. Magota for technical assistance, Y. Fujioka, T. Nakano, and K. Sano at Osaka Medical College for analysis of bacterial morphology, T. Sheen at Edanz Group for editing a draft of this paper, and C. Hidaka for secretarial assistance. The transmission electron microscopic study was supported by E. Oiki and N. Hayakawa at the Center for Medical Research and Education, Graduate School of Medicine, Osaka University. The surface plasmon resonance interaction analysis using Biacore was supported by Y. Ito at the Center for Medical Research and Education, Graduate School of Medicine, Osaka University. This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (A18H040280 and T18K151870), the Japan Agency for Medical Research and Development (JP18gm1010004), and the Terumo Foundation for Life Sciences and Arts.

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R.O. planed and performed experiments and wrote the paper. T.K. and T.I. generated C. rodentium mutant strains. C.C.H. and B.H.S. generated recombinant proteins and performed animal experiments. S.H. performed gene expression analyses. T.K. performed animal experiments. K.T. planned and directed the research.

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Correspondence to Kiyoshi Takeda.

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Okumura, R., Kodama, T., Hsu, C. et al. Lypd8 inhibits attachment of pathogenic bacteria to colonic epithelia. Mucosal Immunol 13, 75–85 (2020).

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