In panel B, Bla g 1 is colored based on similarity to Per a 1, and in panel D, Bla g 5 is colored with respect to similarity to Der p 8

In panel B, Bla g 1 is colored based on similarity to Per a 1, and in panel D, Bla g 5 is colored with respect to similarity to Der p 8. cytokines and chemokines (IL-8, IL-25, IL-33, CCL20 and GM-CSF) [42C44]. Some effects are mediated by anti-TB agent 1 proteases acting on protease-activated receptors (PAR-2) (see also Group 10 section) [45,46]. Additional mechanisms of action have been reported in mouse models. First, German cockroach frass was shown to directly affect neutrophil cytokine production via TLR2, but not TLR4, suggesting an important link between innate and adaptive immunity [47]. Second, activation of the signaling associated with the aryl hydrocarbon receptor (which responds to environmental stimuli and is involved in the pathogenesis of asthma), protected lungs from cockroach-induced inflammation [48]. Third, neonatal mice immunized with -1,3 glucan developed IgA-secreting B cells that suppressed the development of cockroach allergy [49]. Most of these studies were performed with cockroach extracts that are known to be very variable in content [50]. Open in a separate window Figure 1 Proposed mechanisms of cockroach allergyCockroach allergens, belonging to 12 different groups, are carried by particles that are inhaled to the human lung, where they activate innate and adaptive immune responses. Mechanisms involved in the process include: a) disruption of epithelial integrity by proteases (such as Per a 10) that facilitate allergen penetration, b) activation of release of pro-inflammatory cytokines from the epithelium in a PAR-2 dependent manner by proteases, c) allergen interaction with different receptors (some of which contribute to the uptake anti-TB agent 1 of allergens by dendritic cells -TLR, CLR-), and subsequent activation of the adaptive immunity with production of IgE antibodies that bind to the high affinity IgE receptors on mast cells. Numbers indicate the allergen group number. anti-TB agent 1 TLR: Toll like receptors, CLR: C-type lectin receptors including mannose receptors, AhR: Aryl hydrocarbon receptor, DC: dendritic cell; T CD4+ and Th2: T cells; B: B cell; MC: mast cell. In the past 20 years, the identification of twelve groups of cockroach allergens has enabled studies on allergen-specific mechanisms of action. Among these, there is evidence of a role of carbohydrates on the interaction of Bla g 2 with the mannose receptor C-type lectin (CD206) in human circulating fibrocytes. These carbohydrates are predominantly small mannose-terminated glycans with and without fucose and stimulate up-regulation of inflammatory cytokines (TNF-, IL-6) and activation of signaling molecules such as nuclear factor kappa B (NF-kB) [51]. anti-TB agent 1 Effects of group 7 allergens that lead to Th2 polarization include promotion of T cell immunoglobulin mucin domain 4 (TIM4) expression in dendritic cells, down-regulation of toll-like receptor 9 and IL-12 release, induction of T-helper type 2 cytokine release and up-regulation of expression of protease-activated receptors on murine mast cells [52C54]. Cockroach allergens: a heterogeneous group of proteins Twelve groups of cockroach allergens are currently listed in the official Allergen Nomenclature database maintained by the World Health Organization/International Union of Immunological Societies (WHO/IUIS) Sub-Committee (www.allergen.org). These groups comprise allergens with a wide variety of structures and functions summarized in Table 1. Allergens from groups 1, 2 and 10 are excreted into the feaces, which facilitates environmental TIE1 exposure, while others are found predominantly in the bodies [24,39,55,56]. In fact, groups 10, 11 and 12 are digestive enzymes [57]. In contrast, Bla g 4 is expressed only in the adult male reproductive system and transferred to the female within anti-TB agent 1 the spermatophore [58]. Other allergens have functions associated with muscle contraction (groups 6, 7 and 8) or metabolism (groups 3, 5 and 9), and most of these allergens are expected to be released to the environment upon death of the cockroach. Since reviewed in 2014 [5,59], molecular studies have unveiled new structural features of allergens in groups 1, 2 and 5, and.