title: 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.affiliation: ZIEL Research Center for Nutrition and Food Science, CDD Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: von Schillde
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hörmannsperger
authors.forename: Monika
authors.initials: M
authors.lastname: Weiher
authors.forename: Carl-Alfred
authors.initials: CA
authors.lastname: Alpert
authors.forename: Hannes
authors.initials: H
authors.lastname: Hahne
authors.forename: Christine
authors.initials: C
authors.lastname: Bäuerl
authors.forename: Karolien
authors.initials: K
authors.lastname: van Huynegem
authors.forename: Lothar
authors.initials: L
authors.lastname: Steidler
authors.forename: Tomas
authors.initials: T
authors.lastname: Hrncir
authors.forename: Gaspar
authors.initials: G
authors.lastname: Pérez-Martínez
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuster
authors.forename: Dirk
authors.initials: D
authors.lastname: Haller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007778:Lactobacillus / Q000201:enzymology* / Q000276:immunology; D007780:Lacticaseibacillus casei / Q000201:enzymology* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D019936:Probiotics / Q000627:therapeutic use; D021381:Protein Transport; D059748:Proteolysis; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism*
chemical_list: D054357:Chemokine CXCL10; D012697:Serine Endopeptidases; C085783:lactocepin