Influenza Virus-Induced Lung Inflammation Was Modulated by Cigarette Smoke Exposure in Mice

Han, Yan; Ling, Man To; Mao, Huawei; Zheng, Jian; Liu, Ming; Lam, Kwok Tai; Liu, Yuan; Tu, Wenwei; Lau, Yu Lung

doi:10.1371/journal.pone.0086166

Cited by 26 publications

(30 citation statements)

References 55 publications

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“…Similarly, chronic CS exposure also increased MIP-2 and IL-6 at ZT6/12 when compared to controls. However, IL-6 and MIP-2 levels were dampened in CS plus Virus group which could be due to immunosuppressive effects of CS which is in line with recent report in which CS exposure suppressed the production of cytokines and chemokines after pandemic H1N1 or avian H9N2 virus infection in mice 57 . It has been shown that the IAV-mediated inflammatory response begins early on day 3 and remains high until day 5–7 post-infection 58 .…”

Section: Discussionsupporting

confidence: 90%

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

Sundar

Ahmad

Yao

et al. 2015

Sci Rep

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Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.

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Section: Discussionsupporting

confidence: 90%

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

Sundar

Ahmad

Yao

et al. 2015

Sci Rep

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“…Cell isolation and flow cytometry. Cells were isolated from the whole lung by digestion with collagenase and DNase as previously described by us (25). Cells obtained from the whole lungs, mLN, and spleen were washed and incubated with anti-mouse CD16/32 (BioLegend) for blocking.…”

Section: Methodsmentioning

confidence: 99%

Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

Lam

et al. 2015

J Virol

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Secondary Streptococcus pneumoniae infection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. S econdary bacterial infection of the respiratory tract following influenza is a severe complication that often increases morbidity (1). Streptococcus pneumoniae is one of the pathogens that commonly cause the coinfection (2). Pneumococcus is also the major pathogen associated with mortality in both the 1918 Spanish influenza pandemic (3-5) and the 2009 H1N1 pandemic (6, 7). Given this clinical importance, it is imperative that we understand how the host immune response can be modulated after the coinfection.Prior influenza virus infection has been demonstrated to impair the immune defense against subsequent pneumococcal growth and infection (8, 9). For example, influenza virus can desensitize epithelial cells and alveolar macrophages to Toll-like receptor (TLR) signals for defense against bacteria (10). Gamma interferon (IFN-␥) induced by influenza virus can inhibit the phagocytosis of pneumococcus by macrophages (11). The type I IFN induced by influenza virus can impair neutrophils (12) and macrophages (13) in the defense against pneumococcus. Influenza virus can decrease tumor necrosis factor alpha (TNF-␣) production from natural killer cells in the lung, which allows an increase bacterial growth (14).In contrast, how secondary pneumococcal infection after influenza can influence the immune response to the initial influenza virus is relatively less well understood. The host adaptive immune response is largely responsible for controlling the influenza virus infection. It has been reported that coinfection could dysregulate Th17 (15) and gamma/delta T cells (16). However, whether the B cell response would be modulated during the coinfection is still not clear. It is reported that vaccine-induced immunity to influenza virus

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“…The efficiency of the influenza infection was strikingly reduced in mice pretreated with LPS/elastase compared to naïve mice, as revealed by significantly lower viral titers at the peak of viral infection, day 5 and day 7 post infection ( Figure S2) which was also reflected by reduced amounts of viable virus in the lung on day 5 (data not shown). This is likely to be due to the development of a polyclonal antibody response observed upon LPS/elastase treatment ( [37,38] and data not shown). Thus, the response to the influenza infection was not comparable between LPS/elastase pretreated and naive mice, and was therefore not included in the remainder of the study.…”

Section: Influenza-induced Exacerbations Are Characterized By Neutropmentioning

confidence: 97%

Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation

et al. 2014

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For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation

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Influenza Virus-Induced Lung Inflammation Was Modulated by Cigarette Smoke Exposure in Mice

Cited by 26 publications

References 55 publications

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation

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