Early-life antibiotics attenuate regulatory T cell generation and increase the severity of murine house dust mite-induced asthma.

Autor: Adami AJ; Department of Immunology, University of Connecticut Health, Farmington, CT, USA., Bracken SJ; Department of Immunology, University of Connecticut Health, Farmington, CT, USA., Guernsey LA; Department of Immunology, University of Connecticut Health, Farmington, CT, USA.; Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA., Rafti E; Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA., Maas KR; Microbial Analysis, Resources, and Services Facility, University of Connecticut, Storrs, CT, USA., Graf J; Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA., Matson AP; Department of Immunology, University of Connecticut Health, Farmington, CT, USA.; Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA.; Division of Neonatology, Connecticut Children's Medical Center, Hartford, CT, USA., Thrall RS; Department of Immunology, University of Connecticut Health, Farmington, CT, USA., Schramm CM; Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA. cschramm@uchc.edu.; Division of Pulmonary Medicine, Connecticut Children's Medical Center, Hartford, CT, USA. cschramm@uchc.edu.
Jazyk: angličtina
Zdroj: Pediatric research [Pediatr Res] 2018 Sep; Vol. 84 (3), pp. 426-434. Date of Electronic Publication: 2018 Jul 02.
DOI: 10.1038/s41390-018-0031-y
Abstrakt: Introduction: Early-life exposure to antibiotics (ABX) has been linked to increases in asthma severity and prevalence in both children and laboratory animals. We explored the immunologic mechanisms behind this association using a mouse model of house dust mite (HDM)-induced asthma and early-life ABX exposure.
Methods: Mice were exposed to three short courses of ABX following weaning and experimental asthma was thereafter induced. Airway cell counts and differentials; serum immunoglobulin E (IgE); pulmonary function; lung histopathology; pulmonary regulatory T cells (Tregs); and the fecal microbiome were characterized following ABX exposure and induction of experimental asthma.
Results: Asthma severity was increased in mice exposed to ABX, including: airway eosinophilia, airway hyper-reactivity, serum HDM-specific IgE, and lung histopathology. ABX treatment led to sharp reduction in fecal microbiome diversity, including the loss of pro-regulatory organisms such as Lachnospira. Pulmonary Tregs were reduced with ABX treatment, and this reduction was directly proportional to diminished microbiome diversity.
Conclusion: Intermittent exposure to ABX early in life worsened the severity of experimental asthma and reduced pulmonary Tregs; the latter change correlated with decreased microbiome diversity. These data may suggest targets for immunologic or probiotic therapy to counteract the harmful effects of childhood ABX.
Databáze: MEDLINE
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