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Paneth Cell-Derived Lysozyme Defines the Composition of Mucolytic Microbiota and the Inflammatory Tone of the Intestine.

Authors
  • Yu, Shiyan1
  • Balasubramanian, Iyshwarya1
  • Laubitz, Daniel2
  • Tong, Kevin3
  • Bandyopadhyay, Sheila1
  • Lin, Xiang4
  • Flores, Juan1
  • Singh, Rajbir1
  • Liu, Yue1
  • Macazana, Carlos1
  • Zhao, Yanlin5
  • Béguet-Crespel, Fabienne6
  • Patil, Karuna2
  • Midura-Kiela, Monica T2
  • Wang, Daniel1
  • Yap, George S5
  • Ferraris, Ronaldo P7
  • Wei, Zhi4
  • Bonder, Edward M1
  • Häggblom, Max M8
  • And 6 more
  • 1 Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
  • 2 Department of Pediatrics, University of Arizona, Tucson, AZ, USA.
  • 3 Department of Genetics, Rutgers University, Piscataway, NJ, USA.
  • 4 Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, USA. , (Jersey)
  • 5 Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ, USA. , (Jersey)
  • 6 Micalis Institute, Institut National de la Recherche Agronomique (INRA), AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France. , (France)
  • 7 Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, USA. , (Jersey)
  • 8 Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ, USA.
  • 9 Department of Biological Sciences, Rutgers University, Newark, NJ, USA; Department of Pathology, Princeton Medical Center, Plainsboro, NJ, USA.
  • 10 Department of Microbiology and Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, USA.
  • 11 Department of Pediatrics, University of Arizona, Tucson, AZ, USA; Department of Immunobiology, University of Arizona, Tucson, AZ, USA.
  • 12 Department of Biological Sciences, Rutgers University, Newark, NJ, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Electronic address: [email protected] , (Jersey)
Type
Published Article
Journal
Immunity
Publication Date
Aug 18, 2020
Volume
53
Issue
2
Identifiers
DOI: 10.1016/j.immuni.2020.07.010
PMID: 32814028
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Paneth cells are the primary source of C-type lysozyme, a β-1,4-N-acetylmuramoylhydrolase that enzymatically processes bacterial cell walls. Paneth cells are normally present in human cecum and ascending colon, but are rarely found in descending colon and rectum; Paneth cell metaplasia in this region and aberrant lysozyme production are hallmarks of inflammatory bowel disease (IBD) pathology. Here, we examined the impact of aberrant lysozyme production in colonic inflammation. Targeted disruption of Paneth cell lysozyme (Lyz1) protected mice from experimental colitis. Lyz1-deficiency diminished intestinal immune responses to bacterial molecular patterns and resulted in the expansion of lysozyme-sensitive mucolytic bacteria, including Ruminococcus gnavus, a Crohn's disease-associated pathobiont. Ectopic lysozyme production in colonic epithelium suppressed lysozyme-sensitive bacteria and exacerbated colitis. Transfer of R. gnavus into Lyz1-/- hosts elicited a type 2 immune response, causing epithelial reprograming and enhanced anti-colitogenic capacity. In contrast, in lysozyme-intact hosts, processed R. gnavus drove pro-inflammatory responses. Thus, Paneth cell lysozyme balances intestinal anti- and pro-inflammatory responses, with implications for IBD. Copyright © 2020 Elsevier Inc. All rights reserved.

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