WSB1 and IL21R Genetic Variants Are Involved in Th2 Immune Responses to Ascaris lumbricoides.

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

Drought impacts on children's respiratory health in the Brazilian Amazon.

notes: PMCID: PMC3893650types: Journal Article; Research Support, Non-U.S. Gov'tThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Drought conditions in Amazonia are associated with increased fire incidence, enhancing aerosol emissions with degradation in air quality. Quantifying the synergic influence of climate and human-driven environmental changes on human health is, therefore, critical for identifying climate change adaptation pathways for this vulnerable region. Here we show a significant increase (1.2%-267%) in hospitalisations for respiratory diseases in children under-five in municipalities highly exposed to drought. Aerosol was the primary driver of hospitalisations in drought affected municipalities during 2005, while human development conditions mitigated the impacts in 2010. Our results demonstrated that drought events deteriorated children's respiratory health particularly during 2005 when the drought was more geographically concentrated. This indicates that if governments act on curbing fire usage and effectively plan public health provision, as a climate change adaptation procedure, health quality would improve and public expenditure for treatment would decrease in the region during future drought events.Natural Environment Research Council (NERC)Economic and Social Research Council (ESRC