tetano
Editor, Senior Moderator
Respir Res. 2017 Sep 2;18(1):166. doi: 10.1186/s12931-017-0649-z.
[h=1]RIG-I overexpression decreases mortality of cigarette smoke exposed mice during influenza A virus infection.[/h] Wang X[SUP]1[/SUP], Wu W[SUP]1[/SUP], Zhang W[SUP]1[/SUP], Leland Booth J[SUP]1[/SUP], Duggan ES[SUP]1[/SUP], Tian L[SUP]1[/SUP], More S[SUP]2[/SUP], Zhao YD[SUP]3[/SUP], Sawh RN[SUP]4,[/SUP][SUP]5[/SUP], Liu L[SUP]2[/SUP], Zou MH[SUP]6[/SUP], Metcalf JP[SUP]7,[/SUP][SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]METHODS:[/h] 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).
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] 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.
[h=4]KEYWORDS:[/h] Cytokine; Influenza virus; Lung; RIG-I; Smoking; Transgenic mouse
PMID: 28865477 DOI: 10.1186/s12931-017-0649-z
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[h=1]RIG-I overexpression decreases mortality of cigarette smoke exposed mice during influenza A virus infection.[/h] Wang X[SUP]1[/SUP], Wu W[SUP]1[/SUP], Zhang W[SUP]1[/SUP], Leland Booth J[SUP]1[/SUP], Duggan ES[SUP]1[/SUP], Tian L[SUP]1[/SUP], More S[SUP]2[/SUP], Zhao YD[SUP]3[/SUP], Sawh RN[SUP]4,[/SUP][SUP]5[/SUP], Liu L[SUP]2[/SUP], Zou MH[SUP]6[/SUP], Metcalf JP[SUP]7,[/SUP][SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]METHODS:[/h] 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).
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] 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.
[h=4]KEYWORDS:[/h] Cytokine; Influenza virus; Lung; RIG-I; Smoking; Transgenic mouse
PMID: 28865477 DOI: 10.1186/s12931-017-0649-z
Free full text