Chitin Activates Parallel Immune Modules that Direct Distinct Inflammatory Responses via Innate Lymphoid Type 2 and γδ T Cells

Immunity (Impact Factor: 19.75). 03/2014; 40(3). DOI: 10.1016/j.immuni.2014.02.003
Source: PubMed

ABSTRACT Chitin, a polysaccharide constituent of many allergens and parasites, initiates innate type 2 lung inflammation through incompletely defined pathways. We show that inhaled chitin induced expression of three epithelial cytokines, interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP), which nonredundantly activated resident innate lymphoid type 2 cells (ILC2s) to express IL-5 and IL-13 necessary for accumulation of eosinophils and alternatively activated macrophages (AAMs). In the absence of all three epithelial cytokines, ILC2s normally populated the lung but failed to increase IL-5 and IL-13. Although eosinophils and AAMs were attenuated, neutrophil influx remained normal without these epithelial cytokines. Genetic ablation of ILC2s, however, enhanced IL-1β, TNFα, and IL-23 expression, increased activation of IL-17A-producing γδ T cells, and prolonged neutrophil influx. Thus, chitin elicited patterns of innate cytokines that targeted distinct populations of resident lymphoid cells, revealing divergent but interacting pathways underlying the tissue accumulation of specific types of inflammatory myeloid cells.

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    • "IL-33 induction occurred in both hematopoietic and non-hematopoietic cells, particularly in alveolar type 2 cells (Kouzaki et al., 2011; McSorley et al., 2014; R.M.L., unpublished data). Activation of lung ILC2s (Bartemes et al., 2012; Beamer et al., 2013; Doherty et al., 2012; Halim et al., 2012; Van Dyken et al., 2014), Th2 cells (Endo et al., 2015; Kurowska-Stolarska et al., 2008), or both (Iijima et al., 2014), were required to mediate the allergic phenotype , depending on the model system. ILC2s might indirectly support the generation of Th2 cells via IL-13 induction of dendritic cell migration or through direct ILC2/Th2 interactions (Halim et al., 2014; Martinez-Gonzalez et al., 2015; Oliphant et al., 2014). "
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    ABSTRACT: Interleukin-33 (IL-33) is a nuclear-associated cytokine of the IL-1 family originally described as a potent inducer of allergic type 2 immunity. IL-33 signals via the receptor ST2, which is highly expressed on group 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, thus underpinning its association with helminth infection and allergic pathology. Recent studies have revealed ST2 expression on subsets of regulatory T cells, and for a role for IL-33 in tissue homeostasis and repair that suggests previously unrecognized interactions within these cellular networks. IL-33 can participate in pathologic fibrotic reactions, or, in the setting of microbial invasion, can cooperate with inflammatory cytokines to promote responses by cytotoxic NK cells, Th1 cells, and CD8(+) T cells. Here, we highlight the regulation and function of IL-33 and ST2 and review their roles in homeostasis, damage, and inflammation, suggesting a conceptual framework for future studies. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 06/2015; 42(6):1005-1019. DOI:10.1016/j.immuni.2015.06.006 · 19.75 Impact Factor
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    • "Membrane receptor expression and cytokine secretion is elevated when exposed to carbohydrates, glycosides, or glycolipids (Lucas et al. 2010, Sullivan et al. 2010). These molecules interact as ligands with receptors of macrophages (Satoh et al. 2010), eosinophils and basophils (Reese et al. 2007), epithelial cells (Roy et al. 2012) and other cells (Koller et al. 2011, Van Dyken et al. 2014). After recognition of foreign determinants, cascade signaling is induced which determines the outcome of the immune response. "
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    Acta Parasitologica 06/2015; 60(2). DOI:10.1515/ap-2015-0047 · 0.97 Impact Factor
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    ABSTRACT: A study by Halim and Steer (2014) in this issue of Immunity shows that innate lymphoid cells type 2 (ILC2s) are crucial for inducing adaptive T helper 2 immunity by providing interleukin-13. Another study by van Dyken et al. (2014) shows that ILC2s control eosinophilia and alternative activation of macrophages.
    Immunity 03/2014; 40(3):313-4. DOI:10.1016/j.immuni.2014.02.010 · 19.75 Impact Factor
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