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From the Cover: TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection

来自 国家科技图书文献中心

阅读量：

90

作者：

JR Aldridge，CE Moseley，DA Boltz，NJ Negovetich，PG Thomas

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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 prol if era tor-activated receptor-γ 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.

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关键词：

H5N1 inflammation pathogenesis

DOI：

10.1073/pnas.0900655106

被引量：

721

年份：

2009

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来源期刊

Proceedings of the National Academy of Sciences
2009/04/01

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2011
被引量：110

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