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RATIONALE: Aryl hydrocarbon receptor (AhR), a receptor for common environmental contaminants, is an important regulator of immune responses. Our previous studies have suggested a role of AhR in protecting against cockroach allergen-induced lung inflammation by using AhR-/mice. Autophagy plays a major role in controlling immune responses and inflammation. We sought to determine whether the activated AhR signaling specifically in airway epithelium by cockroach allergen modulates cockroach allergen-induced lung inflammation through autophagy METHODS: The role of AhR expressed in epithelium in cockroach allergen (CRE) induced allergic inflammation was investigated in a mouse model of asthma with AhR epithelial conditional knock out mice (ftpc-Cre;AhR flox/flox). Cockroach allergen induced the activation of AhR and autophagy signaling in epithelium was determined. The role of autophagy in CRE-induced asthma was also investigated. RESULTS: CRE-challenged Sftpc-Cre; AhR flox/flox mice displayed decreased lung infiltrates, mucus production, and airway hyper-responsiveness. These mice also showed reduced levels of IL-4, IL-5, IL-13, IL-17, but increased IL-10 and IL-22 in the BAL fluids. Decreased IC3B II in airways was also observed. Moreover, CRE can activate AhR (CYP1A1 and CYP1B1) and autophagy (Beclin-1, Atg5, and p62) signaling in epithelial cells in vitro, and AhR agonist TCDD can potentiate CRE-induced autophagy. Furthermore, CRE-induced lung inflammation was significantly suppressed when autophagy inhibitor was used in the mouse model with decreased lung infiltrates and Th2/T17 cytokines in BAL fluids. CONCLUSIONS: Contrast to the protective role previously observed in AhR-/mice, AhR in airway epithelial may exacerbate CRE-induced inflammation, which may through activating autophagy signaling.

Genetic and epigenetic factors are considered to be critical for host-parasite interactions. There are limited data on the role of such factors during human infections with Ascaris lumbricoides. Here, we describe the potential role of genetic factors as determinants of the Th2 immune response to A. lumbricoides in Brazilian children. Stool samples were collected from the children to detect A. lumbricoides by microscopy and peripheral blood leukocytes (PBLs) were cultured in whole blood cultures for detection of cytokines (IL-5, IL-10, and IL-13) in vitro. Levels of anti-A. lumbricoides IgE and IgG4 were measured in plasma. DNA was extracted from PBLs and genotyped using Illumina 2.5 Human Omni Beadchip. Candidate genes associated with A. lumbricoides responses were identified and SNVs in these selected genes associated with the Th2 immune response to A. lumbricoides. Haplotype, gene expression, and epigenetic analyses were done to identify potential associations with Th2 immune responses. GWAS on samples from 1,189 children identified WSB1 as a candidate gene, and IL-21R was selected as a biologically relevant linked gene for further analysis. Variants in WSB1 and IL21R were associated with markers of Th2 immune responses: increased A. lumbricoides-specific IgE and IL-5/IL-13 by PBLs from infected compared to uninfected individuals. In infected children, WSB1 but not IL21R gene expression was suppressed and increased methylation was observed in the WSB1 promoter region. This is the first study to show an association between genetic variants in WSB1 and IL21R and Th2 immune responses during A. lumbricoides infections in children. WSB1/IL21R pathways could provide a potential target for the treatment of Th2-mediated diseases.

A reação imunoenzimática - ELISA foi empregada na sorologia da Wuchereriose, utilizando como antígeno extrato bruto de verme adulto de Setaria equina. Foram estudados soros de 139 indivíduos em três grupos: grupo 1 - de pacientes com diagnóstico parasitológico de Wuchereriose; grupo 2 - de pacientes com diversas patologias; grupo 3 - de pessoas clinicamente normais, de área endêmica e não endêmica. O antígeno utilizado mostrou alta comunidade antigênica coma W. bancrofti. As reações cruzadas, obtidas em particular com soros de pacientes com parasitoses intestinais (áscaris, ancilóstoma) recomendam a investigação de frações antigênicas de Setaria equina que possam fornecer testes de maior especificidade.