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

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

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

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.

Original languageEnglish
Pages (from-to)387-396
Number of pages10
JournalCell Host and Microbe
Volume11
Issue number4
DOIs
StatePublished - 19 Apr 2012

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