Early Postnatal Secondhand Smoke Exposure Disrupts Bacterial Clearance and Abolishes Immune Responses in Muco-Obstructive Lung Disease
Secondhand smoke (SHS) exposure has been linked to the worsening of ongoing lung diseases. However, whether SHS exposure affects the manifestation and natural history of imminent pediatric muco-obstructive airway diseases such as cystic fibrosis remains unclear. To address these questions, we exposed transgenic (-Tg) mice to SHS from postnatal day (PND) 3-21 and lung phenotypes were examined at PND22. Although a majority of filtered air (FA)-exposed -Tg (FA-Tg) mice successfully cleared spontaneous bacterial infections by PND22, the SHS-exposed -Tg (SHS-Tg) mice failed to resolve these infections. This defect was associated with suppressed antibacterial defenses, i.e., phagocyte recruitment, IgA secretion, and Muc5b expression. Whereas the FA-Tg mice exhibited marked mucus obstruction and responses, SHS-Tg mice displayed a dramatic suppression of these responses. Mechanistically, downregulated expression of IL-33, a stimulator of type II innate lymphoid cells, in lung epithelial cells was associated with suppression of neutrophil recruitment, IgA secretions, responses, and delayed bacterial clearance in SHS-Tg mice. Cessation of SHS exposure for 21 d restored previously suppressed responses, including phagocyte recruitment, IgA secretion, and mucous cell metaplasia. However, in contrast with FA-Tg mice, the SHS-Tg mice had pronounced epithelial necrosis, alveolar space consolidation, and lymphoid hyperplasia; indicating lagged unfavorable effects of early postnatal SHS exposure in later life. Collectively, our data show that early postnatal SHS exposure reversibly suppresses IL-33 levels in airspaces which, in turn, results in reduced neutrophil recruitment and diminished response. Our data indicate that household smoking may predispose neonates with muco-obstructive lung disease to bacterial exacerbations.
Publication Source (Journal or Book title)
Journal of immunology (Baltimore, Md. : 1950)
Lewis, B. W., Sultana, R., Sharma, R., Noël, A., Langohr, I., Patial, S., Penn, A. L., & Saini, Y. (2017). Early Postnatal Secondhand Smoke Exposure Disrupts Bacterial Clearance and Abolishes Immune Responses in Muco-Obstructive Lung Disease. Journal of immunology (Baltimore, Md. : 1950), 199 (3), 1170-1183. https://doi.org/10.4049/jimmunol.1700144