Chitin Particles are Multifaceted Immune Adjuvants.
Summary of "Chitin Particles are Multifaceted Immune Adjuvants."
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.
We hypothesized that chitin is an important adjuvant for adaptive immunity.
Mice were injected with a solution of ovalbumin and chitin.
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 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-gamma 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 while IL-17 and TLR-2 were required for cytokine elaboration. IL-17A also inhibited the generation of adaptive Th1 responses.
These studies demonstrate that chitin is a potent multi-faceted 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.
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut, United States.
This article was published in the following journal.
Name: American journal of respiratory and critical care medicine
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20656945
- DOI: http://dx.doi.org/10.1164/rccm.200912-1877OC
Medical and Biotech [MESH] Definitions
An enzyme that converts UDP glucosamine into chitin and UDP. EC 184.108.40.206.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
Elementary Particle Interactions
The interactions of particles responsible for their scattering and transformations (decays and reactions). Because of interactions, an isolated particle may decay into other particles. Two particles passing near each other may transform, perhaps into the same particles but with changed momenta (elastic scattering) or into other particles (inelastic scattering). Interactions fall into three groups: strong, electromagnetic, and weak. (From McGraw-Hill Encyclopedia of Science & Technology, 7th ed)
The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.
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