The role of innate immunity receptors in the pathogenesis of inflammatory bowel disease.

Paula Peruzzi Elia,Heitor Siffert Pereira De Souza,Claudio Bernardazzi,Yolanda Faia M Tolentino

doi:10.1155/2015/936193

Abstract

Innate immunity constitutes the first line of defense, fundamental for the recognition and the initiation of an inflammatory response against microorganisms. The innate immune response relies on the sensing of microbial-associated molecular patterns through specialized structures such as toll-like receptors (TLRs) and the nucleotide oligomerization domain- (NOD-) like receptors (NLRs). In the gut, these tasks are performed by the epithelial barrier and the presence of adaptive and innate immune mechanisms. TLRs and NLRs are distributed throughout the gastrointestinal mucosa, being more expressed in the epithelium, and in lamina propria immune and nonimmune cells. These innate immunity receptors exhibit complementary biological functions, with evidence for pathways overlapping. However, as tolerance is the predominant physiological response in the gastrointestinal mucosa, it appears that the TLRs are relatively downregulated, while NLRs play a critical role in mucosal defense in the gut. Over the past two decades, genetic polymorphisms have been associated with several diseases including inflammatory bowel disease. Special emphasis has been given to the susceptibility to Crohn's disease, in association with abnormalities in the NOD2 and in the NLRP3/inflammasome. Nevertheless, the mechanisms underlying innate immune receptors dysfunction that result in the persistent inflammation in inflammatory bowel disease remain to be clarified.

Highlights

In the gastrointestinal system, homeostasis represents a rather complex and dynamic process, with a critical role for mucosal immunity
TLR5 is basically expressed in the colonic epithelium and recognizes invasive flagellated bacteria, while TLR2 and TLR4 are present in low levels in the intestinal epithelium, more abundantly in the colonic crypts [18]
Currently, in addition to early sensing of pathogens and delivering and immediate response, the innate immune system is implicated in the regulation and shaping of the adaptive immune response

Summary

Introduction

Homeostasis represents a rather complex and dynamic process, with a critical role for mucosal immunity. It is expected that the host identifies and responds appropriately to the luminal contents of the gastrointestinal tract. In this regard, the epithelium, constituted by a single cell lining, plays an important role separating an essentially sterile internal milieu from a formidable burden of microbes that populate the gastrointestinal tract [1]. The interaction between the gut and the microorganisms that constitute the resident microbiota is tightly regulated and has evolved in the course of several million years [3] This mutualistic relationship between host and microbiota is thought to be essential for the immune homeostasis and is well balanced in normal conditions [4, 5].

Innate Immunity in the Intestine

Toll-Like Receptors in the Intestine

NOD-Like Receptors and Inflammasome in the Intestine

Defective Innate Immunity in IBD

Conclusion