Research On Biological Function And Immunoregulation Mechanism Of CXCL4 In Mice Upon Respiratory Infection With Influenza A H1N1

Influenza is an acute respiratory infection which caused by the A, B, C three types of influenza virus (influenza virus, IAV). As the disease spread through the air, and influenza virus is prone to antigenic variation, the crowds are generally susceptible to variants, so it is easy to quickly lead to a worldwide pandemic. The current avian influenza outbreaks and is widespread among another countries in the world, it will undoubtedly increase the chances of avian flu and human influenza virus when gene recombination occurs, it will also increase the risk of a new influenza virus strain emerging. Undoubtedly, influenza virus will cause for next global human flu pandemic in the future, it is just a matter of time.Influenza adaptive animals are idea models of IAV infection in exploring respiratory diseases and the immune response. Successful models of IAV infection include mice, rats, ferrets, pigs and primates, monkeys and other animals. A specific gene knockout mouse advance the analysis of gene function upon infection. Given CXCL4 involving a varity of immune cell function in the body role, such as in many physiological and pathological inflammatory reactions, blood coagulation and so on., We established the model of CXCL4 knock IAV infection mice and explored the biological effects of CXCL4 upon IAV infection.The results showed that CXCL4 exerted a protective effect against respiratory challenge with the fatal H1N1 virus in mice. CXCL4 knockout resulted in a diminished viral clearance capacity in the infected mouse lungs, which caused severe inflammation lung damage and edema during late infection, leading to a rapid loss of body weight and a high mortality rate in the mice following infection. Additionally, CXCL4 knockout caused a significant decrease in neutrophils but a relative increase in monocytes/macrophages of the innate immune system in lung bronchoalveolar lavage fluid collected from mice during initial infection. However, CXCL4 knockout did not affect the adaptive immune responses of T and B lymphocytes at late infection. Further study revealed that the CXCL4 knockout inhibited neutrophil recruitment to the infected mouse lung tissue without affecting the generation of neutrophils in the bone marrow. Thus, the above results demonstrate an important protective role of CXCL4 in respiratory influenza virus infection. CXCL4 exerts an antiviral immunological effect by facilitating neutrophil infiltration into influenza virus-infected lung tissue.