Chitin, chitinases and chitinase-like proteins in allergic inflammation and tissue remodeling

Abstract

Chitin, the second most abundant polysaccharide in nature after cellulose, consist exoskeleton of lower organisms such as fungi, crustaceans and insects except mammals. Recently, several studies evaluated immunologic effects of chitin in vivo and in vitro and revealed new aspects of chitin regulation of innate and adaptive immune responses. It has been shown that exogenous chitin activates macrophages and other innate immune cells and also modulates adaptive type 2 allergic inflammation. These studies further demonstrate that chitin stimulate macrophages by interacting with different cell surface receptors such as macrophage mannose receptor, toll-like receptor 2 (TLR-2), C-type lectin receptor Dectin-1, and leukotriene B4 receptor (BLT1). On the other hand, a number of chitinase or chitinase-like proteins (C/CLP) are ubiquitously expressed in the airways and intestinal tracts from insects to mammals. In general, these chitinase family proteins confer protective functions to the host against exogenous chitin-containing pathogens. However, substantial body of recent studies also set light on new roles of C/CLP in the development and progression of allergic inflammation and tissue remodeling. In this review, recent findings on the role of chitin and C/CLP in allergic inflammation and tissue remodeling will be highlighted and controversial and unsolved issues in this field of studies will be discussed.

Keywords: Chitin; chitinase-like proteins; chitinases; immunity; remodeling.

Fig. 1

Chitin stimulation of innate immune cells and regulation of adaptive allergic immune responses. Chitin or chitin derivatives activate macrophages to express a number of pro-inflammatory cytokines, chemokine (e.g., GCP-2) and other mediators (LTB4) via macrophage mannose receptor, TLR-2, and C-type lectin receptor. Then the eosinophils, basophils and neutrophils that are recruited by these inflammatory mediators present type II allergic responses by secretion of Th2 cytokines (IL-4, IL-5, IL-13) and other allergic mediators (histamines, peroxidases). Thus, chitin-induced eosinophils and basophils further enhance allergen-induced adaptive Th2 inflammatory responses. On the other hand, many studies also support that chitin activates macrophages, NK cells and neutrophils to produce type I cytokines (TNF-α, IL-12, IL-1β and IFN-γ), and suppress allergen-induced adaptive type II immune responses. Chitosan down-regulate allergen-induced TSLP expression from epithelial cells, and inhibits Th2 polarization by TSLP-dendritic cell interaction. The direct effect of chitin and chitin derivatives on dendritic cells remains to be determined.