Severe Pneumonia Caused by Coinfection With Influenza Virus Followed by Methicillin-Resistant Staphylococcus aureus Induces Higher Mortality in Mice

Frontiers in Immunology

卷:9

Binghua Zhu¹  Hao Li²  Jiangyun Zhao³  Weiguang Guo³  Shan Wang³  Peng Li³  Yuan Liang³  Ligui Wang³  Xiao Liu³  Chaojie Yang³  Hongbin Song³  Leili Jia³  Rongzhang Hao³  Hongbo Liu³  Jing Xie³  Shaofu Qiu³  Pengwei Long⁴  Yong Jiang⁵  Hui Ma⁶ 

[1] 305 Hospital of PLA, Beijing, China;

[2] Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China;

[3] Chinese PLA Center for Disease Control and Prevention, Beijing, China;

[4] Department of Health Care, Chinese PLA Joint Staff Headquarters Guard Bureau, Beijing, China;

[5] Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China;

[6] The 6th Medical Center of Chinese PLA General Hospital, Beijing, China;

关键词: coinfection;    influenza;    methicillin-resistant Staphylococcus aureus;    bacteria;    pneumonia;   

DOI  :  10.3389/fimmu.2018.03189

来源: DOAJ

【 摘 要 】

Background: Coinfection with influenza virus and bacteria is a major cause of high mortality during flu pandemics. Understanding the mechanisms behind such coinfections is of utmost importance both for the clinical treatment of influenza and the prevention and control of epidemics.Methods: To investigate the cause of high mortality during flu pandemics, we performed coinfection experiments with H1N1 influenza virus and Staphylococcus aureus in which mice were infected with bacteria at time points ranging from 0 to 7 days after infection with influenza virus.Results: The mortality rates of mice infected with bacteria were highest 0–3 days after infection with influenza virus; lung tissues extracted from these co-infected mice showed higher infiltrating cells and thicker lung parenchyma than lung samples from coinfected mice in which influenza virus was introduced at other times and sequences. The levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-6 in the 0–3 day coinfected group were significantly higher than those in the other groups (p < 0.01), as were the mRNA levels of IFN-γ, IL-6, and TNF-α. Coinfection with influenza virus and S. aureus led to high mortality rates that are directly dependent on the sequence and timing of infection by both pathogens. Moreover, coinfection following this particular schedule induced severe pneumonia, leading to increased mortality.Conclusions: Our data suggest that prevention of bacterial co-infection in the early stage of influenza virus infection is critical to reducing the risk of clinical mortality.

【 授权许可】

Unknown