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  3. Sialylation shapes mucus architecture inhibiting bacterial invasion in the colon

Sialylation shapes mucus architecture inhibiting bacterial invasion in the colon

  • Mucosal Immunol. 2023 Oct;16(5):624-641. doi: 10.1016/j.mucimm.2023.06.004.
Mugen Taniguchi 1,  Ryu Okumura 2,  Takahisa Matsuzaki 3,  Ayaka Nakatani 4,  Kei Sakaki 5,  Shota Okamoto 6,  Airi Ishibashi 6,  Haruka Tani 6,  Momoka Horikiri 7,  Naritaka Kobayashi 8,  Hiroshi Y Yoshikawa 7,  Daisuke Motooka 9,  Daisuke Okuzaki 10,  Shota Nakamura 11,  Toshiyuki Kida 12,  Akihiko Kameyama 13,  Kiyoshi Takeda 14
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Infectious Diseases Unit, Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
  • 2 Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; Institute for Open and Transdisciplinary Research Initiative, Osaka University, Osaka, Japan.
  • 3 Center for Future Innovation, Graduate School of Engineering, Osaka University, Osaka, Japan; Department of Applied Physics, Graduate School of Engineering, Osaka University, Osaka, Japan.
  • 4 Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • 5 Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • 6 Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
  • 7 Department of Applied Physics, Graduate School of Engineering, Osaka University, Osaka, Japan.
  • 8 Department of Electronic Systems Engineering, The University of Shiga Prefecture, Shiga, Japan.
  • 9 Institute for Open and Transdisciplinary Research Initiative, Osaka University, Osaka, Japan; Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • 10 WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • 11 Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • 12 Institute for Open and Transdisciplinary Research Initiative, Osaka University, Osaka, Japan; Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Osaka, Japan.
  • 13 Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki, Japan.
  • 14 Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; Institute for Open and Transdisciplinary Research Initiative, Osaka University, Osaka, Japan; Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan. Electronic address: ktakeda@ongene.med.osaka-u.ac.jp.
PMID: 37385587 DOI: 10.1016/j.mucimm.2023.06.004
Abstract

In the intestine, Mucin 2 (Muc2) forms a network structure and prevents Bacterial invasion. Glycans are indispensable for Muc2 barrier function. Among various glycosylation patterns of Muc2, sialylation inhibits bacteria-dependent Muc2 degradation. However, the mechanisms by which Muc2 creates the network structure and sialylation prevents Mucin degradation remain unknown. Here, by focusing on two glycosyltransferases, St6 N-acetylgalactosaminide α-2,6-sialyltransferase 6 (St6galnac6) and β-1,3-galactosyltransferase 5 (B3galt5), mediating the generation of desialylated glycans, we show that sialylation forms the network structure of Muc2 by providing negative charge and hydrophilicity. The colonic mucus of mice lacking St6galnac6 and B3galt5 was less sialylated, thinner, and more permeable to microbiota, resulting in high susceptibility to intestinal inflammation. Mice with a B3galt5 mutation associated with inflammatory bowel disease (IBD) also showed the loss of desialylated glycans of mucus and the high susceptibility to intestinal inflammation, suggesting that the reduced sialylation of Muc2 is associated with the pathogenesis of IBD. In mucins of mice with reduced sialylation, negative charge was reduced, the network structure was disturbed, and many bacteria invaded. Thus, sialylation mediates the negative charging of Muc2 and facilitates the formation of the Mucin network structure, thereby inhibiting Bacterial invasion in the colon to maintain gut homeostasis.

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