文章基本信息

标题：TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection
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作者：Jerry R. Aldridge ; Carson E. Moseley ; David A. Boltz 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：13
页码：5306-5311
DOI：10.1073/pnas.0900655106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Respiratory infection with highly pathogenic influenza A viruses is characterized by the exuberant production of cytokines and chemokines and the enhanced recruitment of innate inflammatory cells. Here, we show that challenging mice with virulent influenza A viruses, including currently circulating H5N1 strains, causes the increased selective accumulation of a particular dendritic cell subset, the tipDCs, in the pneumonic airways. These tipDCs are required for the further proliferation of influenza-specific CD8+ T cells in the infected lung, because blocking their recruitment in CCR2-/- mice decreases the numbers of CD8+ effectors and ultimately compromises virus clearance. However, diminution rather than total elimination of tipDC trafficking by treatment with the peroxisome proliferator-activated receptor-{gamma} agonist pioglitazone moderates the potentially lethal consequences of excessive tipDC recruitment without abrogating CD8+ T cell expansion or compromising virus control. Targeting the tipDCs in this way thus offers possibilities for therapeutic intervention in the face of a catastrophic pandemic.
关键词：H5N1 ; inflammation ; pathogenesis