Cytokine and chemokine profiles in lung tissues from fatal cases of 2009 pandemic influenza A (H1N1): role of the host immune response in pathogenesis.
Pathological studies on fatal cases caused by 2009 pandemic influenza H1N1 virus (2009 pH1N1) reported extensive diffuse alveolar damage and virus infection predominantly in the lung parenchyma. However, the host immune response after severe 2009 pH1N1 infection is poorly understood. Herein, we investigated viral load, the immune response, and apoptosis in lung tissues from 50 fatal cases with 2009 pH1N1 virus infection. The results suggested that 7 of the 27 cytokines/chemokines showed remarkably high expression, including IL-1 receptor antagonist protein, IL-6, tumor necrosis factor-α, IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein 1-β, and interferon-inducible protein-10 in lung tissues of 2009 pH1N1 fatal cases. Viral load, which showed the highest level on day 7 of illness onset and persisted until day 17 of illness, was positively correlated with mRNA levels of IL-1 receptor antagonist protein, monocyte chemoattractant protein-1, macrophage inflammatory protein 1-β, interferon-inducible protein-10, and regulated on activation normal T-cell expressed and secreted. Apoptosis was evident in lung tissues stained by the TUNEL assay. Decreased Fas and elevated FasL mRNA levels were present in lung tissues, and cleaved caspase-3 was frequently seen in pneumocytes, submucosal glands, and lymphoid tissues. The pathogenesis of the 2009 pH1N1 virus infection is associated with viral replication and production of proinflammatory mediators. FasL and caspase-3 are involved in the pathway of 2009 pH1N1 virus-induced apoptosis in lung tissues, and the disequilibrium between the Fas and FasL level in lung tissues could contribute to delayed clearance of the virus and subsequent pathological damages.
Department of Influenza, State Key Laboratory for Molecular Virology and Genetic Engineering, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Rongbao
R
Gao
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Julu
J
Bhatnagar
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Dianna M
DM
Blau
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Patricia
P
Greer
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Dominique C
DC
Rollin
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Amy M
AM
Denison
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Marlene
M
Deleon-Carnes
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Wun-Ju
WJ
Shieh
Immunology and Pathogenesis Branch, the Influenza Division, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Suryaprakash
S
Sambhara
Immunology and Pathogenesis Branch, the Influenza Division, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Terrence M
TM
Tumpey
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Mitesh
M
Patel
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Lindy
L
Liu
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Christopher
C
Paddock
Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Clifton
C
Drew
Department of Influenza, State Key Laboratory for Molecular Virology and Genetic Engineering, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Yuelong
Y
Shu
Immunology and Pathogenesis Branch, the Influenza Division, the Centers for Disease Control and Prevention, Atlanta, Georgia.
Jacqueline M
JM
Katz
Department of Influenza, State Key Laboratory for Molecular Virology and Genetic Engineering, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Infectious Diseases Pathology Branch, the Division of High-Consequence Pathogens and Pathology, the Centers for Disease Control and Prevention, Atlanta, Georgia. Electronic address: szaki@cdc.gov.
Sherif R
SR
Zaki
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D058873:Pandemics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019562:Viral Load; D055815:Young Adult
D018925:Chemokines; D012333:RNA, Messenger; D053148:Caspase 3