Prenatal tobacco smoke exposure predisposes offspring mice to exacerbated allergic airway inflammation associated with altered innate effector function

Maria Ferrini,Kent Pinkerton,Zeina Jaffar,Britten Postma,Sophia Carvalho,Yoon Hee Cho,Lucas Miranda Marques,Kevan Roberts

doi:10.1186/s12989-017-0212-6

Abstract

BackgroundEpidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma.MethodsPregnant C57BL/6 mice were exposed to either ETS or filtered air throughout gestation and the effect on pulmonary inflammation in the offspring were examined and compared. Specifically, the effects on eosinophilic inflammation, airway hyperreactivity, goblet cell hyperplasia, properties of pulmonary natural killer (NK) cells and type 2 cytokines elicited in response to inhaled house dust mite (HDM) allergen were investigated in the progeny.ResultsExposure to ETS prenatally significantly exacerbated HDM-induced airway eosinophilic inflammation, hyperreactivity, mucus secretion, cysteinyl leukotriene biosynthesis and type 2 cytokine production in the offspring. Consistently, lung mononuclear cells from ETS-exposed offspring secreted higher levels of IL-13 when stimulated in vitro with anti-αβ TCR antibody or HDM allergen. Moreover, offspring from ETS-exposed dams exhibited a higher frequency of CD11b+ dendritic cells and CD3+CD4+ T lymphocytes in the lungs following allergen inhalation compared to air-exposed mice. Unexpectedly, the exacerbated allergic inflammation in the ETS-exposed offspring was associated with a reduction in CD3−CD19−NK1.1+CD94+ NK cell numbers and their IFN-γ production, highlighting a role for altered innate immunity in the enhanced allergic response.ConclusionOur results reveal that prenatal exposure to ETS predisposes offspring to an exacerbated allergic airway inflammation that is associated with a reduction in pulmonary NK cell function, suggesting that NK cells play a key role in controlling asthma severity.

Highlights

Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease
This study provides important insight into how prenatal environmental tobacco smoke (ETS) exposure influences susceptibility to allergic asthma and suggests that natural killer (NK) cells play a key role in modulating this process
The adverse effects of prenatal exposure to ETS or filtered air on pulmonary inflammation was assessed in both adult and juvenile offspring mice after an acute sensitization and challenge with intranasal house dust mite (HDM) allergen over a period of two weeks using a model of allergic asthma that we have previously developed [15]

Summary

Introduction

Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. While genetic factors contribute to susceptibility and development of asthma, the increased disease prevalence cannot be completely explained on the basis of genetics. Accumulating epidemiological evidence suggests that environmental factors, such as air pollution and exposure to secondhand or environmental tobacco smoke (ETS), are key contributors in the development of childhood asthma [5,6,7]. Smoke exposure during fetal development and in the early years of a child’s life is strongly associated with respiratory tract infections and asthma that can persist into adulthood [9]. Despite continuing efforts to reduce smoking prevalence, over one billion people worldwide remain smokers, with globally half of all children estimated to be exposed to secondhand smoke [13]

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