Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines.

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.

• Authors: Marie-Anne von Schillde, Gabriele Hörmannsperger, Monika Weiher, Carl-Alfred Alpert, Hannes Hahne, Christine Bäuerl, Karolien van Huynegem, Lothar Steidler, Tomas Hrncir, Gaspar Pérez-Martínez, Bernhard Kuster, Dirk Haller
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 11 Issue 4 Pg. 387-96 (Apr 19 2012) ISSN: 1934-6069 [Electronic] United States
• PMID: 22520466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Chemokine CXCL10
• Serine Endopeptidases
• lactocepin

Topics

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