Microbial exposures protect mice from experimental allergic asthma via innate immunity in murine models. This study was to see if there was a link between early life innate immunity and asthma development in children at risk. N=445 children from the PASTURE farm birth cohort assessed their natural, Th2, Th1, and Th17 cytokine expression after PBMCs with lipopolysaccharide (LPS) stimulation. Single-nucleotide polymorphisms at the 17q21 asthma gene locus were used to identify children at risk of asthma. The SNP rs7216389 in the GSDMB gene was used specifically. The researchers used Weekly diaries to track wheezing in the first year of life, and a questionnaire was used to assess asthma at the age of six.
After LPS stimulation, not all cytokines were detectable in all children. Carrying the 17q21 risk allele rs7216389 was related to the risk of wheezing only in the class with the lowest amount of LPS-induced activation, odds ratio (OR)=1.89, 95%-CI 1.13-3.16, p=0.015, when grading detectability of cytokines using latent class analysis. In contrast, no link between the 17q21 risk allele and wheeze (OR=0.63, 95%-CI 0.29-1.40, p=0.258, p=0.034 for interaction) or school-age asthma was found in children with significant cytokine activation after LPS stimulation. Consumption of unprocessed cow’s milk was linked to increased cytokine activation in these children (OR=3.37, 95%-CI 1.56-7.30, p=0.002), mediated in part by the gut microbiome. These data imply that activated immune responses following innate stimulation, partly mediated by a gut-immune axis, can reduce asthma risk in those with the 17q21 gene.
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