Prenatal tobacco smoke exposure predisposes offspring mice to exacerbated allergic airway inflammation associated with a
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RESEARCH
Open Access
Prenatal tobacco smoke exposure predisposes offspring mice to exacerbated allergic airway inflammation associated with altered innate effector function Maria Ferrini1, Sophia Carvalho1, Yoon Hee Cho1, Britten Postma1, Lucas Miranda Marques1, Kent Pinkerton2, Kevan Roberts1*† and Zeina Jaffar1*†
Abstract Background: 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. 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. Methods: Pregnant 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. Results: Exposure 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. Conclusion: Our 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. Keywords: Prenatal exposure, Environmental tobacco smoke, Allergic asthma, Innate immunity
* Correspondence: [email protected]; [email protected] † Equal contributors 1 Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, College of Health Professions and Biomedical Sciences, University of Montana, Missoula, MT MT 59812, USA Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.o
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