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Single cell transcriptomics reveals cell type specific features of developmentally regulated responses to lipopolysaccharide between birth and 5 yearsHuman perinatal life is characterized by a period of extraordinary change during which newborns encounter abundant environmental stimuli and exposure to potential pathogens. To meet such challenges, the neonatal immune system is equipped with unique functional characteristics that adapt to changing conditions as development progresses across the early years of life, but the molecular characteristics of such adaptations remain poorly understood.
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Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of lifeAppropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group.
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Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels.
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Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways.
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Innate Immune Training for Prevention of Recurrent Wheeze in Early ChildhoodPat Deborah Holt Strickland PhD, DSc, FRCPath, FRCPI, FAA PhD Emeritus Honorary Researcher Head, Pregnancy and Early Life Immunology Patrick.Holt@
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IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced ReprogrammingHigh risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high versus low susceptibility to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype.