Chitin particles are multifaceted immune adjuvants.
BACKGROUND
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.


OBJECTIVE
We hypothesized that chitin is an important adjuvant for adaptive immunity.


METHODS
Mice were injected with a solution of ovalbumin and chitin.


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(+) T cells from mice sensitized with ovalbumin plus chitin were incubated with ovalbumin-stimulated bone marrow-derived dendritic cells. In these experiments, CD4(+) T-cell proliferation, IL-5, IL-13, IFN-γ, and IL-17A production were appreciated. Toll-like 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.
Da Silva
Carla A
CA
Yale University School of Medicine, New Haven, CT 06519-1612, USA.
Pochard
Pierre
P
Lee
Chun Geun
CG
Elias
Jack A
JA
D056704:Adaptive Immunity / Q000187:drug effects* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002686:Chitin / Q000494:pharmacology*; D004195:Disease Models, Animal; D007111:Immunity, Cellular / Q000187:drug effects*; D020381:Interleukin-17 / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology
D000276:Adjuvants, Immunologic; D020381:Interleukin-17; D051195:Toll-Like Receptor 2; D002686:Chitin