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

@article{citeulike:4368516, abstract = {10.1073/pnas.0900655106 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-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.}, author = {Aldridge, Jerry R. and Moseley, Carson E. and Boltz, David A. and Negovetich, Nicholas J. and Reynolds, Cory and Franks, John and Brown, Scott A. and Doherty, Peter C. and Webster, Robert G. and Thomas, Paul G.}, citeulike-article-id = {4368516}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0900655106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/13/5306.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/13/5306.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19279209}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19279209}, day = {31}, doi = {10.1073/pnas.0900655106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {dendritic, influenza, innate}, month = {March}, number = {13}, pages = {5306--5311}, posted-at = {2009-04-20 10:15:54}, priority = {2}, title = {TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection}, url = {http://dx.doi.org/10.1073/pnas.0900655106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4368516 L3 - citeulike-article-id:4368516 N2 - 10.1073/pnas.0900655106 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-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. IS - 13 JF - Proceedings of the National Academy of Sciences EP - 5311 TI - TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection VL - 106 SP - 5306 KW - dendritic KW - influenza KW - innate AU - Aldridge, Jerry AU - Moseley, Carson AU - Boltz, David AU - Negovetich, Nicholas AU - Reynolds, Cory AU - Franks, John AU - Brown, Scott AU - Doherty, Peter AU - Webster, Robert AU - Thomas, Paul PY - 2009/03/31/ UR - http://dx.doi.org/10.1073/pnas.0900655106 ER -