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Active thrombin produced by the intestinal epithelium controls mucosal biofilms

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11140-w

2041-1723

Jean‐Paul Motta, Alexandre Denadai‐Souza, David Sagnat, Laura Guiraud, Anissa Edir, Chrystelle Bonnart, Mireille Sebbag, Perrine Rousset, Ariane Lapeyre, Carine Séguy, Noa Mathurine-Thomas, Heather J. Galipeau, Delphine Bonnet, Laurent Alric, André G. Buret, John L. Wallace, Antoine Dufour, Elena F. Verdú, Morley D. Hollenberg, Éric Oswald, Matteo Sérino, Céline Deraison, Nathalie Vergnolle,

Neonatal and Maternal Infections

Abstract Proteolytic homeostasis is important at mucosal surfaces, but its actors and their precise role in physiology are poorly understood. Here we report that healthy human and mouse colon epithelia are a major source of active thrombin. We show that mucosal thrombin is directly regulated by the presence of commensal microbiota. Specific inhibition of luminal thrombin activity causes macroscopic and microscopic damage as well as transcriptomic alterations of genes involved in host-microbiota interactions. Further, luminal thrombin inhibition impairs the spatial segregation of microbiota biofilms, allowing bacteria to invade the mucus layer and to translocate across the epithelium. Thrombin cleaves the biofilm matrix of reconstituted mucosa-associated human microbiota. Our results indicate that thrombin constrains biofilms at the intestinal mucosa. Further work is needed to test whether thrombin plays similar roles in other mucosal surfaces, given that lung, bladder and skin epithelia also express thrombin.