TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection
Jerry R Aldridge, Carson E Moseley, David A Boltz, Nicholas J Negovetich, Cory Reynolds, John Franks, Scott A Brown, Peter C Doherty, Robert G Webster, Paul G Thomas
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2009
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, di..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services
Awarded by NATIONAL CANCER INSTITUTE
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
We thank Hui-Ling Yen and Jacco Boon for advice; Richard Webby for the DKO virus; Scott Krauss, Melissa Morris, Richard Cross, James Knowles, Jennifer Rogers, Ashley Webb, Yolanda Griffin, and Cedric Proctor for excellent technical assistance; Ray Kuhn and Sharon Naron for editorial assistance; Julie Groff for assistance with Fig. S1; and the World Health Organization Global Influenza Surveillance Network for providing the H5N1 viruses. The authors dedicate this manuscript to the memory of our good friend and colleague, the late Cedric Proctor. Cedric's support in our high-containment facility was critical for completion of the present study. This work was supported by Contract HHSN266200700005C from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, and by the American Lebanese Syrian Associated Charities.