Chitin and Its Effects on Inflammatory and Immune Responses

Abstract

Chitin, a potential allergy-promoting pathogen-associated molecular pattern (PAMP), is a linear polymer composed of N-acetylglucosamine residues which are linked by β-(1,4)-glycosidic bonds. Mammalians are potential hosts for chitin-containing protozoa, fungi, arthropods, and nematodes; however, mammalians themselves do not synthetize chitin and thus it is considered as a potential target for recognition by mammalian immune system. Chitin is sensed primarily in the lungs or gut where it activates a variety of innate (eosinophils, macrophages) and adaptive immune cells (IL-4/IL-13 expressing T helper type-2 lymphocytes). Chitin induces cytokine production, leukocyte recruitment, and alternative macrophage activation. Intranasal or intraperitoneal administration of chitin (varying in size, degree of acetylation and purity) to mice has been applied as a routine approach to investigate chitin's priming effects on innate and adaptive immunity. Structural chitin present in microorganisms is actively degraded by host true chitinases, including acidic mammalian chitinases and chitotriosidase into smaller fragments that can be sensed by mammalian receptors such as FIBCD1, NKR-P1, and RegIIIc. Immune recognition of chitin also involves pattern recognition receptors, mainly via TLR-2 and Dectin-1, to activate immune cells to induce cytokine production and creation of an immune network that results in inflammatory and allergic responses. In this review, we will focus on various immunological aspects of the interaction between chitin and host immune system such as sensing, interactions with immune cells, chitinases as chitin degrading enzymes, and immunologic applications of chitin.

Keywords: Adaptive immunity; Chitin; Chitinase; Immune system; Innate immunity.

Fig. 1

Chitin-binding receptors from various superfamilies sense chitin fragments through different pathways and activate signaling. FIBCD1 binds chitin and directs acetylated components for degradation in the cytoplasmic endosomes through endocytosis. Dectin-1 through its signaling induces the respiratory burst and phagocytosis. TLR-2 signaling mediated by TIR domain results in inducing IL-12 and TNF production similar to Dectin-1. Mannose receptors participate in endocytosis of chitinous materials along with formation of endosomes. Mannose receptors in a pH-dependent manner dissociate from ligands and recycle back to the plasma membrane

Fig. 2

Large chitin polymers from chitin containing organisms are inert but under chitinolytic activity of AMCase produce intermediate fragments successfully sensed by chitin-binding receptors on the surface of macrophages. Each receptor depending on activation pathway induces specific cytokines

Fig. 3

Infection by chitin-containing nematode results in the release of IL-33, IL-25, and TSLP from airway epithelium which activate ILC-2 cells. The later cells produce Th2 cytokines IL-4, IL-5, and IL-13 by which Th2 and eosinophil activation occur. Macrophage and mast cell contribute to further ILC2 activation by producing PGD2 and LTD4

Fig. 4

TLR expression and cytokine production patterns after chitin exposure to evaluate chitin bioactivity

Fig. 5

Adjuvant property of chitin assessed using TLR2, TLR4, MyD88, IL-17A null mice, and control C57BL/6. In vivo and in vitro investigations were carried on each group after being exposed with alum or chitin fragments. MyD88 and IL-17 were found to have a key role in chitin responses. Further cytokine assays revealed that chitin possess a high capacity to act as adjuvant to induct adaptive Th2, Th1, and Th17 immune responses