Maternal allergen exposure increases offspring sensory airway innervation and airway hyperreactivity in mice

Background: Maternal asthma causes airway hyperreactivity in infants at birth and increases asthma risk in childhood. Humans with severe asthma have increased sensory nerve density in airways. Aim: We investigated whether maternal allergen exposure affects airway reactivity and innervation in their adult offspring. Methods: Female C57BI/6 mice were exposed to house dust mite (HDM) or vehicle (VEH) daily for 4 weeks prior to pregnancy and throughout gestation. At 8 weeks of age, offspring were sensitized and challenged with HDM. 24 hours after final challenge, mice were anesthetized and ventilated, and changes in serotonin-induced bronchoconstriction were measured. Inflammatory cells, Th2 cytokines, and neurotrophins were measured in bronchoalveolar lavage (BAL). Sensory nerve length and branching was quantified in airway epithelium. Results: Following HDM sensitization and challenge, offspring from HDM exposed mothers had significantly increased airway hyperreactivity, eosinophils and macrophages compared with offspring from VEH exposed mothers. IL-5 and IL-13 were not different in BAL of offspring from HDM vs VEH exposed mothers. Offspring from HDM exposed mothers had increased sensory nerve length and branching in airway epithelium and increased brain-derived neurotrophic factor compared with offspring from VEH exposed mothers. Conclusions: Exposure to maternal antigen in utero increases sensory innervation and neurotrophin expression in airways of their offspring. Subsequent exposure of these offspring to antigen results in significantly greater airway hyperreactivity, and macrophage and eosinophilic inflammation. NIH grant support: HL132414, HL124165, HL065228, HL083808