Lactocepin Secreted by Lactobacillus Exerts Anti-Inflammatory Effects by Selectively Degrading Proinflammatory Chemokines

Cell Host Microbe. 2012 Apr 19;11(4):387-96. doi: 10.1016/j.chom.2012.02.006.

Abstract

The intestinal microbiota has been linked to inflammatory bowel diseases (IBD), and oral treatment with specific bacteria can ameliorate IBD. One bacterial mixture, VSL#3, containing Lactobacillus, Bifidobacterium, and Streptococcus, was clinically shown to reduce inflammation in IBD patients and normalize intestinal levels of IP-10, a lymphocyte-recruiting chemokine, in a murine colitis model. We identified Lactobacillus paracasei prtP-encoded lactocepin as a protease that selectively degrades secreted, cell-associated, and tissue-distributed IP-10, resulting in significantly reduced lymphocyte recruitment after intraperitoneal injection in an ileitis model. A human Lactobacillus casei isolate was also found to encode lactocepin and degrade IP-10. L. casei feeding studies in a murine colitis model (T cell transferred Rag2(-/-) mice) revealed that a prtP-disruption mutant was significantly less potent in reducing IP-10 levels, T cell infiltration and inflammation in cecal tissue compared to the isogenic wild-type strain. Thus, lactocepin-based therapies may be effective treatments for chemokine-mediated diseases like IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL10 / metabolism*
  • Colitis / immunology
  • Colitis / metabolism*
  • Colitis / microbiology
  • Colitis / therapy
  • Disease Models, Animal
  • Female
  • Humans
  • Lactobacillus / enzymology*
  • Lactobacillus / immunology
  • Lactobacillus casei / enzymology*
  • Lactobacillus casei / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Probiotics / therapeutic use
  • Protein Transport
  • Proteolysis
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / metabolism*

Substances

  • Chemokine CXCL10
  • Serine Endopeptidases
  • lactocepin