Chitin Particles Are Multifaceted Immune Adjuvants

Abstract

Rationale: Chitin is a ubiquitous polysaccharide in fungi, insects, allergens, and parasites that is released at sites of infection. Its role in the generation of tissue inflammation, however, is not fully understood. Objectives: We hypothesized that chitin is an important adjuvant for adaptive immunity. Methods: Mice were injected with a solution of ovalbumin and chitin. Measurements and Main Results: We used in vivo and ex vivo/in vitro approaches to characterize the ability of chitin fragments to foster adaptive immune responses against ovalbumin and compared these responses to those induced by aluminum hydroxide (alum). In vivo, ovalbumin challenge caused an eosinophil-rich pulmonary inflammatory response, Th2 cytokine elaboration, IgE induction, and mucus metaplasia in mice that had been sensitized with ovalbumin plus chitin or ovalbumin plus alum. Toll-like receptor-2, MyD88, and IL-17A played critical roles in the chitin-induced responses, and MyD88 and IL-17A played critical roles in the alum-induced responses. In vitro, CD4 1 T cells from mice sensitized with ovalbumin plus chitin were incubated with ovalbumin-stimulated bone marrowderived dendritic cells. In these experiments, CD4 1 T-cell proliferation, IL-5, IL-13, IFN-g, and IL-17A production were appreciated. Tolllike receptor-2, MyD88, and IL-17A played critical roles in these in vitro adjuvant properties of chitin. TLR-2 was required for cell proliferation, whereas IL-17 and TLR-2 were required for cytokine elaboration. IL-17A also inhibited the generation of adaptive Th1 responses.Conclusions: These studies demonstrate that chitin is a potent multifaceted adjuvant that induces adaptive Th2, Th1, and Th17 immune responses. They also demonstrate that the adjuvant properties of chitin are mediated by a pathway(s) that involves and is regulated by TLR-2, MyD88, and IL-17A.

The Influence of Chitin on the Immune Response to the House Dust Mite Allergen Blo t 12

“…Our findings differed from those reported by da Silva et al [25 ]in an ovalbumin airway hypersensitivity model where chitin coadministration was necessary to induce airway allergic inflammation and sensitization. Since Blo t 12 isoforms without any adjuvant elicited strong humoral responses, airway hyperreactivity and inflammation, it seems that the marked proallergenic effects of chitin described previously [24,25] were masked by the intrinsic inflammatory potential of this allergen group, which is not observed in immunologically ‘inert' molecules such as ovalbumin when administered alone [48].…”

“…Since Blo t 12 isoforms without any adjuvant elicited strong humoral responses, airway hyperreactivity and inflammation, it seems that the marked proallergenic effects of chitin described previously [24,25] were masked by the intrinsic inflammatory potential of this allergen group, which is not observed in immunologically ‘inert' molecules such as ovalbumin when administered alone [48]. Intrinsic capacities to induce allergic airway inflammation or Th2 activation have been described for a few allergens and have been related to their biochemical properties [15,49,50].…”

“…It has been shown that this carbohydrate can induce airway inflammation in animal models [24]. When coadministered with ovalbumin, it behaves as an adjuvant, boosting IgE production [25]. Chitin is sensed by different innate immune receptors in mammals, including TLR-2 and mannose receptors found in dendritic cells and macrophages [22].…”

Inmunorregulación inducida por helmintos: una actualización

“…Es probable que, aparte del componente proteico, otros tipos de biomoléculas tengan una influencia directa en la estimulación de la IgE de una manera linfocito T-independiente. La quitina es un componente no-proteico (carbohidrato), abundante en parásitos y algunas fuentes de alérge-nos, que puede influir en la producción de IgE (58,59). Los niveles de IgG4 aumentan en condiciones que promueven procesos de inmunorregulación intensa.…”

“…En estudios de reinfección por Schistosoma spp., los niveles de IgG4 específica se han encontrado más bajos en los individuos resistentes que en los susceptibles (64). No obstante, estos anticuerpos parecen ser importante en prevenir la inmunopatología asociada a la destrucción tisular desencadenada por el parásito, pues en algunos tipos de filariasis, los individuos infectados con títulos más altos de IgG4 desarrollan un cuadro clínico menos grave (58,64).…”