Chitin Is a Size-Dependent Regulator of Macrophage TNF and IL-10 Production

Abstract

Chitin is a ubiquitous polysaccharide in fungi, insects, and parasites. We hypothesized that chitin is a size-dependent regulator of innate immunity. To test this hypothesis, we characterized the effects of chitins of different sizes on murine bronchoalveolar or peritoneal macrophages. In these studies, large chitin fragments were inert, while both intermediate-sized chitin (40–70 μm) and small chitin (SC; <40 μm, largely 2–10 μm) stimulated TNF elaboration. In contrast, only SC induced IL-10 elaboration. The effects of intermediate-sized chitin were mediated by pathways that involve TLR2, dectin-1, and NF-κB. In contrast, the effects of SC were mediated by TLR2-dependent and -independent, dectin-1-dependent pathways that involved the mannose receptor and spleen tyrosine kinase. Chitin contains size-dependent pathogen-associated molecular patterns that stimulate TLR2, dectin-1, and the mannose receptor, differentially activate NF-κB and spleen tyrosine kinase, and stimulate the production of pro- and anti-inflammatory cytokines.

AMCase is a crucial regulator of type 2 immune responses to inhaled house dust mites

“…It has also been shown that the size of chitosan was important for phagocytosis (19,20). In fact, the differential role of the size of chitin was supported by another report (21). In our system, chitosan indeed seemed to induce more IL-1β production than chitin in vitro, probably due to the easier accessibility of chitosan to the cells, which might derive from the different solubility between chitin and chitosan, but chitin itself also significantly induced IL-1β ( Fig.…”

“…It is interesting that chitins of different sizes have different effects both in vivo and in vitro (19,21). It was previously reported that intranasal administration of chitin beads induced infiltration of IL-4-expressing cells in lung, but administration of chitin beads that were pretreated with recombinant AMCase failed to induce infiltration of IL-4-expressing cells in lung (11).…”

“…The role of chitin in the immune system is very controversial (19,21,37,38). One of the main reasons for this controversy is that it is difficult to extensively purify chitin (37,38).…”

“…These reports support our observations that enzymatically inactive AMCase-ED mice showed enhanced infiltration of eosinophils in lung and type 2 immune responses after administration of HDM or chitin. It is interesting that small chitin (less than 40 μm) induced IL-10 production in vitro and in vivo (21), suggesting that cleaved chitin may play an inhibitory role in inflammatory responses. However, production of IL-10 by small chitin was increased in cytochalasin D-treated macrophages, and thus this may be independent of caspase-1 and caspase-7 pathways.…”

Chitosan but Not Chitin Activates the Inflammasome by a Mechanism Dependent upon Phagocytosis

“…Most published studies on chitin and chitosan used preparations derived from crustacean sources (16,20), as in our studies, although some have used chitin isolated from fungi (19,38). There are known structural differences between the two sources (39) that could have an impact on how the particles effect the immunological response.…”