Cytokine and Chemokine Profiles in Lung Tissues from Fatal Cases of 2009 Pandemic Influenza A (H1N1) Role of the Host Immune Response in Pathogenesis

被引：90

作者：

Gao, Rongbao ^{[1
]}

Bhatnagar, Julu ^{[2
]}

Blau, Dianna M. ^{[2
]}

Greer, Patricia ^{[2
]}

Rollin, Dominique C. ^{[2
]}

Denison, Amy M. ^{[2
]}

Deleon-Carnes, Marlene ^{[2
]}

Shieh, Wun-Ju ^{[2
]}

Sambhara, Suryaprakash ^{[3
,4
]}

Tumpey, Terrence M. ^{[3
,4
]}

Patel, Mitesh ^{[2
]}

Liu, Lindy ^{[2
]}

Paddock, Christopher ^{[2
]}

Drew, Clifton ^{[2
]}

Shu, Yuelong ^{[1
]}

Katz, Jacqueline M. ^{[3
,4
]}

Zaki, Sherif R. ^{[1
,2
]}

机构：

[1] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, State Key Lab Mol Virol & Genet Engn, Dept Influenza,Chinese Natl Influenza Ctr, Beijing, Peoples R China

[2] Ctr Dis Control & Prevent, Infect Dis Pathol Branch, Influenza Div, Atlanta, GA 30333 USA

[3] Ctr Dis Control & Prevent, Div High Consequence Pathogens & Pathol, Influenza Div, Atlanta, GA 30333 USA

[4] Ctr Dis Control & Prevent, Immunol & Pathogenesis Branch, Influenza Div, Atlanta, GA 30333 USA

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2013年 / 183卷 / 04期

关键词：

CELL-DEATH APOPTOSIS; HONG-KONG INFLUENZA; VIRUS-INFECTION; FAS LIGAND; RESPIRATORY-FAILURE; T-CELLS; EXPRESSION; DISEASE; INDUCTION; PATHOLOGY;

D O I：

10.1016/j.ajpath.2013.06.023

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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-alpha, IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein 1-beta, 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-beta, 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.

引用

页码：1258 / 1268

页数：11

共 61 条

[21] INCREASED CONCENTRATIONS OF INTERLEUKIN-6 AND INTERLEUKIN-1 RECEPTOR ANTAGONIST AND DECREASED CONCENTRATIONS OF BETA-2-GLYCOPROTEIN-I IN GAMBIAN CHILDREN WITH CEREBRAL MALARIA [J].