H5N1 and 1918 Pandemic Influenza Virus Infection Results in Early and Excessive Infiltration of Macrophages and Neutrophils in the Lungs of Mice

PLoS Pathogens

Jacqueline M. Katz¹  Adolfo García-Sastre²  Terrence M. Tumpey³  Lucy A. Perrone⁴  Julie K. Plowden⁴ 

[1] Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York, United States of America;Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America;Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York, United States of America;Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Collaborating Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

关键词: Macrophages;    H5N1;    Influenza viruses;    Respiratory infections;    Cytokines;    Dendritic cells;    Viral pathogens;    Mouse models;   

DOI  :  10.1371/journal.ppat.1000115

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Fatal human respiratory disease associated with the 1918 pandemic influenza virus and potentially pandemic H5N1 viruses is characterized by severe lung pathology, including pulmonary edema and extensive inflammatory infiltrate. Here, we quantified the cellular immune response to infection in the mouse lung by flow cytometry and demonstrate that mice infected with highly pathogenic (HP) H1N1 and H5N1 influenza viruses exhibit significantly high numbers of macrophages and neutrophils in the lungs compared to mice infected with low pathogenic (LP) viruses. Mice infected with the 1918 pandemic virus and a recent H5N1 human isolate show considerable similarities in overall lung cellularity, lung immune cell sub-population composition and cellular immune temporal dynamics. Interestingly, while these similarities were observed, the HP H5N1 virus consistently elicited significantly higher levels of pro-inflammatory cytokines in whole lungs and primary human macrophages, revealing a potentially critical difference in the pathogenesis of H5N1 infections. These results together show that infection with HP influenza viruses such as H5N1 and the 1918 pandemic virus leads to a rapid cell recruitment of macrophages and neutrophils into the lungs, suggesting that these cells play a role in acute lung inflammation associated with HP influenza virus infection. In addition, primary macrophages and dendritic cells were also susceptible to 1918 and H5N1 influenza virus infection in vitro and in infected mouse lung tissue.

【 授权许可】

CC BY