Editors' ChoiceInfectious Disease

A firsthand view of how secondhand smoke disrupts airway immunity

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Science Translational Medicine  25 Apr 2018:
Vol. 10, Issue 438, eaat4478
DOI: 10.1126/scitranslmed.aat4478

Abstract

Chronic tobacco smoke exposure exacerbates Haemophilus influenzae infection by disrupting innate and adaptive immune responses in mice.

Exposure to tobacco secondhand smoke (SHS) kills an estimated 600,000 people each year and confers an increased risk of acute respiratory infections and chronic obstructive pulmonary disease (COPD). The molecular basis for these epidemiologic connections, however, remain incompletely understood. Bhat et al. address this gap in knowledge by developing and studying a murine model of chronic smoke exposure and infection with Haemophilus influenzae, an important pathogen implicated in both pneumonia and acute COPD exacerbations.

The authors first examined the pathophysiologic effects of smoke exposure on host response to H. influenzae and observed augmented proinflammatory cytokine release and excessive airway tissue injury. Further experiments revealed a disruption of innate immune responses characterized by increased neutrophils, reduced macrophages, and impaired bacterial pathogen clearance. Next, the authors investigated impacts on adaptive immunity and found that smoke exposure suppressed antigen-specific T cells and impaired production of anti-Heamophilus antibodies. This led them to subsequently examine the impacts of SHS on immune response following vaccination with a Heamophilus antigen. Compared with mice maintained in clean air, those with prior SHS exposure had impaired antibody responses and when challenged with acute Haemophilus infection, had impaired bacterial clearance. Last, the authors investigated whether these defects in immunity persisted even after smoke exposure was stopped and mice were relocated to a clean air environment. Even after eight weeks of recovery, the mice demonstrate continued abnormalities in inflammation and immunity, suggesting a long-lasting detrimental effect.

While this work is an important step toward understanding how environmental exposures modulate host defense against infection, several key outstanding questions remain. These include clarifying how realistically this murine model recapitulates human SHS exposure, examining the impacts of SHS and infection on a metagenomic level, and determining whether similar effects result from exposure to other ambient environmental toxins, such as e-cigarette vapor and particulate matter air pollution.

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