Chitin induces accumulation in tissue of innate immune cells associated with allergy

Abstract

Antigens associated with insects, crustacea, helminths and fungi make up a considerable proportion of the environmental antigens associated with allergies and asthma in humans. Nonetheless, the common elements that link these widely distributed entities remain unknown. A major culprit might be chitin. Chitin is the second most abundant polymer in nature, providing the osmotic stability and tensile strength to countless cell walls and rigid exoskeletons. Reese et al. have now found that mice treated with chitin develop an allergic response, characterized by a build-up of interleukin-4 expressing innate immune cells. Treatment with a chitinase enzyme abolishes the response. Occupations associated with high environmental chitin levels, such as shellfish processors, are prone to high incidences of asthma, suggesting that this pathway may play a role in human allergic disease. The biopolymer chitin is one of the main components in the cell walls of fungi, the exoskeletons of insects and crustaceans and the bodies of some parasitic worms. This paper describes how chitin elicits an innate allergic response in mice, which is controlled by a host chitinase. Allergic and parasitic worm immunity is characterized by infiltration of tissues with interleukin (IL)-4- and IL-13-expressing cells, including T-helper-2 cells, eosinophils and basophils1. Tissue macrophages assume a distinct phenotype, designated alternatively activated macrophages2. Relatively little is known about the factors that trigger these host responses. Chitin, a widespread environmental biopolymer of N-acetyl-β-d-glucosamine, provides structural rigidity to fungi, crustaceans, helminths and insects3. Here, we show that chitin induces the accumulation in tissue of IL-4-expressing innate immune cells, including eosinophils and basophils, when given to mice. Tissue infiltration was unaffected by the absence of Toll-like-receptor-mediated lipopolysaccharide recognition but did not occur if the injected chitin was pre-treated with the IL-4- and IL-13-inducible mammalian chitinase, AMCase4, or if the chitin was injected into mice that overexpressed AMCase. Chitin mediated alternative macrophage activation in vivo and the production of leukotriene B4, which was required for optimal immune cell recruitment. Chitin is a recognition element for tissue infiltration by innate cells implicated in allergic and helminth immunity and this process can be negatively regulated by a vertebrate chitinase.