Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 48, Pages 13833-13838Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1611400113
Keywords
mucin; colon; inflammation; obesity; peptidoglycan
Categories
Funding
- Swedish Research Council
- Swedish Cancer Foundation
- Knut and Alice Wallenberg Foundation
- IngaBritt
- Arne Lundberg Foundation
- Sahlgren's University Hospital (LUAALF)
- Wilhelm and Martina Lundgren's Foundation
- Wiberg Foundation
- Torsten Soderbergs Stiftelse
- Sahlgrenska Academy
- National Institute of Allergy and Infectious Diseases [U01AI095473]
- Swedish Foundation for Strategic Research-The Mucus-Bacteria-Colitis Center of the Innate Immunity Program
- European Union Marie Curie
- Human Frontiers
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The distal colon functions as a bioreactor and harbors an enormous amount of bacteria in a mutualistic relationship with the host. The microbiota have to be kept at a safe distance to prevent inflammation, something that is achieved by a dense inner mucus layer that lines the epithelial cells. The large polymeric nets made up by the heavily O-glycosylated MUC2 mucin forms this physical barrier. Proteomic analyses of mucus have identified the lectin-like protein ZG16 (zymogen granulae protein 16) as an abundant mucus component. To elucidate the function of ZG16, we generated recombinant ZG16 and studied Zg16(-/-) mice. ZG16 bound to and aggregated Gram-positive bacteria via binding to the bacterial cell wall peptidoglycan. Zg16(-/-)mice have a distal colon mucus layer with normal thickness, but with bacteria closer to the epithelium. Using distal colon explants mounted in a horizontal perfusion chamber we demonstrated that treatment of bacteria with recombinant ZG16 hindered bacterial penetration into the mucus. The inner colon mucus of Zg16(-/-) animals had a higher load of Gram-positive bacteria and showed bacteria with higher motility in the mucus close to the host epithelium compared with cohoused littermate Zg16(+/+). The more penetrable Zg16(-/-) mucus allowed Gram-positive bacteria to translocate to systemic tissues. Viable bacteria were found in spleen and were associated with increased abdominal fat pad mass in Zg16(-/-) animals. The function of ZG16 reveals a mechanism for keeping bacteria further away from the host colon epithelium.
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