Title |
RIG-I overexpression decreases mortality of cigarette smoke exposed mice during influenza A virus infection
|
---|---|
Published in |
Respiratory Research, September 2017
|
DOI | 10.1186/s12931-017-0649-z |
Pubmed ID | |
Authors |
Xiaoqiu Wang, Wenxin Wu, Wei Zhang, J. Leland Booth, Elizabeth S. Duggan, Lili Tian, Sunil More, Yan D. Zhao, Ravindranauth N. Sawh, Lin Liu, Ming-Hui Zou, Jordan P. Metcalf |
Abstract |
Retinoic acid-inducible gene I (RIG-I) is an important regulator of virus-induced antiviral interferons (IFNs) and proinflammatory cytokines which participate in clearing viral infections. Cigarette smoke (CS) exposure increases the frequency and severity of respiratory tract infections. We generated a RIG-I transgenic (TG) mouse strain that expresses the RIG-I gene product under the control of the human lung specific surfactant protein C promoter. We compared the mortality and host immune responses of RIG-I TG mice and their litter-matched wild type (WT) mice following challenge with influenza A virus (IAV). RIG-I overexpression increased survival of IAV-infected mice. CS exposure increased mortality in WT mice infected with IAV. Remarkably, the effect of RIG-I overexpression on survival during IAV infection was enhanced in CS-exposed animals. CS-exposed IAV-infected WT mice had a suppressed innate response profile in the lung compared to sham-exposed IAV-infected WT mice in terms of the protein concentration, total cell count and inflammatory cell composition in the bronchoalveolar lavage fluid. RIG-I overexpression restored the innate immune response in CS-exposed mice to that seen in sham-exposed WT mice during IAV infection, and is likely responsible for enhanced survival in RIG-I TG mice as restoration preceded death of the animals. Our results demonstrate that RIG-I overexpression in mice is protective for CS enhanced susceptibility of smokers to influenza infection, and that CS mediated RIG-I suppression may be partially responsible for the increased morbidity and mortality of the mice exposed to IAV. Thus, optimizing the RIG-I response may be an important treatment strategy for CS-enhanced lung infections, particularly those due to IAV. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 40% |
Colombia | 1 | 20% |
Unknown | 2 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 6 | 21% |
Student > Bachelor | 5 | 18% |
Student > Doctoral Student | 3 | 11% |
Student > Postgraduate | 3 | 11% |
Student > Ph. D. Student | 2 | 7% |
Other | 2 | 7% |
Unknown | 7 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 8 | 29% |
Veterinary Science and Veterinary Medicine | 3 | 11% |
Biochemistry, Genetics and Molecular Biology | 3 | 11% |
Nursing and Health Professions | 2 | 7% |
Immunology and Microbiology | 2 | 7% |
Other | 2 | 7% |
Unknown | 8 | 29% |