Inflammation and emphysema in cigarette smoke-exposed mice when instilled with poly (I:C) or infected with influenza A or respiratory syncytial viruses.

Getahun E Agga,Yohannes A Mebratu,Yohannes Tesfaigzi,Kevin R Smith

doi:10.1186/s12931-016-0392-x

Abstract

BackgroundThe length of time for cigarette smoke (CS) exposure to cause emphysema in mice is drastically reduced when CS exposure is combined with viral infection. However, the extent of inflammatory responses and lung pathologies of mice exposed to CS and infected with influenza A virus (IAV), respiratory syncytial virus (RSV), or treated with the viral derivative dsRNA (polyinosine-polycytidylic acid [poly (I:C)] have not been compared.MethodsMice were exposed to CS or filtered air for 4 weeks and received a single dose of vehicle, AV, or RSV infection and extent of inflammation and emphysema was evaluated 14 d later. In another set of experiments, mice were instilled with poly (I:C) twice a week during the third and fourth weeks of CS exposure and immediately analyzed for extent of inflammation and lung pathologies.ResultsIn CS-exposed mice, inflammation was characterized mainly by macrophages, lymphocytes, and neutrophils after IAV infection, mainly by lymphocytes, and neutrophils after RSV infection, and mainly by lymphocytes and neutrophils after poly (I:C) instillations. Despite increased inflammation, extent of emphysema by poly (I:C) was very mild; but was robust and similar for both IAV and RSV infections with enhanced MMP-12 mRNA expression and TUNEL positivity. Both IAV and RSV infections increased the levels of IL-17, IL-1β, IL-12b, IL-18, IL-23a, Ccl-2, Ccl-7 mRNAs in the lungs of CS-exposed mice with IAV causing more increases than RSV.ConclusionCS-induced inflammatory responses and extent of emphysematous changes differ depending on the type of viral infection. These animal models may be useful to study the mechanisms by which different viruses exacerbate CS-induced inflammation and emphysema.

Highlights

The length of time for cigarette smoke (CS) exposure to cause emphysema in mice is drastically reduced when CS exposure is combined with viral infection
CS-induced inflammatory responses and extent of emphysematous changes differ depending on the type of viral infection
We found that Influenza A Virus (IAV) significantly reduced body weight in both filtered air (FA)- and CS-exposed mice (Fig. 2a)

Summary

Introduction

The length of time for cigarette smoke (CS) exposure to cause emphysema in mice is drastically reduced when CS exposure is combined with viral infection. Interactions between CS exposure and viral infection induce exaggerated inflammatory and tissue remodeling responses [28, 29]. Viral infections, such as IAV [30,31,32] and respiratory syncytial virus (RSV) [19, 24, 25] are associated with acute COPD exacerbations, but the severity of infection in patients with COPD depends on both viral and host factors [33]. RSV accounts for a quarter of all viral-induced COPD exacerbations [19, 24, 25] and is an important respiratory pathogen in the elderly, in those with chronic lung diseases such as COPD [23,24,25]. To understand disease progression and develop better therapies, establishing animal models that reflect these conditions in humans is crucial

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