Innate immune signalling at intestinal mucosal surfaces: a... : Current Opinion in Gastroenterology (original) (raw)

Immunology: Edited by W. Allan Walker

Innate immune signalling at intestinal mucosal surfaces: a fine line between host protection and destruction

Division of Gastroenterology and Hepatology, University Hospital of Essen, and Medical School, University of Duisburg-Essen, Essen, Germany

Correspondence to Elke Cario, MD, Division of Gastroenterology and Hepatology, University Hospital of Essen, Institutsgruppe I, Virchowstr. 171, D-45147 Essen, Germany Tel/fax: +49 201 723 4527; e-mail: [email protected]

Abstract

Purpose of review

Emerging evidence underscores that inappropriate innate immune responses driven by commensals contribute to the pathogenesis of chronic inflammatory bowel diseases in genetically susceptible hosts. The present review focuses on defining the recently described mechanistic functions through which the innate immune signalling apparatus shapes mucosal homeostasis of the intestine in health and disease.

Recent findings

Commensal-induced innate immune signalling actively drives at least six major interdependent functions to control homeostasis in the healthy intestinal mucosa: 1) barrier preservation, 2) inhibition of apoptosis and inflammation, 3) acceleration of wound repair and tissue regeneration, 4) exclusion of harmful pathogens through autophagy and other antimicrobial defenses, while 5) maintaining immune tolerance towards harmless commensals, and 6) linkage to adaptive immunity. Any disturbance of this peaceful and mutually beneficial host–commensal relationship may imbalance innate immune signalling, which predisposes to chronic intestinal inflammation and associated tumourigenesis in inflammatory bowel diseases.

Summary

Recent advances have highlighted the complex mechanistics and functional diversity of innate immunity that paradoxically mediate both protective and destructive responses in the intestinal mucosa. Related signalling targets may offer novel therapeutic approaches in the treatment of inflammatory bowel diseases and inflammation-related cancer.