Abstract
Rationale: In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Objectives: Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. Methods: In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in n = 445 children. Children at risk of asthma were defined based on single-nucleotide polymorphisms at the 17q21 asthma gene locus. Specifically, we used the SNP rs7216389 in the GSDMB gene. Wheeze in the first year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years. Measurements and Main Results: Not all cytokines were detectable in all children after LPS stimulation. When classifying detectability of cytokines by latent class analysis, carrying the 17q21 risk allele rs7216389 was associated with risk of wheeze only in the class with the lowest level of LPS-induced activation: odds ratio (OR), 1.89; 95% confidence interval [CI], 1.13-3.16; P = 0.015. In contrast, in children with high cytokine activation after LPS stimulation, no association of the 17q21 risk allele with wheeze (OR, 0.63; 95% CI, 0.29-1.40; P = 0.258, P = 0.034 for interaction) or school-age asthma was observed. In these children, consumption of unprocessed cow's milk was associated with higher cytokine activation (OR, 3.37; 95% CI, 1.56-7.30; P = 0.002), which was in part mediated by the gut microbiome. Conclusions: These findings suggest that within the 17q21 genotype, asthma risk can be mitigated by activated immune responses after innate stimulation, which is partly mediated by a gut-immune axis.
Original language | English |
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Pages (from-to) | 641-650 |
Number of pages | 10 |
Journal | American journal of respiratory and critical care medicine |
Volume | 205 |
Issue number | 6 |
Early online date | 17 Dec 2021 |
DOIs | |
Publication status | Published - 17 Dec 2021 |
Bibliographical note
A complete list of the PASTURE Study Group members may be found before the beginning of the References.The PASTURE study was supported by the European Commission (research grants QLK4-CT-2001-00250, FOOD-CT-2006-31708, and KBBE-2007-2-2-06), and the European Research Council (grant 250268). P.L. and F.M.F. receive funding from the Scottish Government Rural and Environment Sciences and Analytical Services Division.
Keywords
- 17q21 genotype
- farm environment
- gut microbiome
- innate immune response in children
- unprocessed cow’s milk