tetano
Editor, Senior Moderator
Am J Pathol. 2011 Oct 13. [Epub ahead of print]
Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection.
Damjanovic D, Divangahi M, Kugathasan K, Small CL, Zganiacz A, Brown EG, Hogaboam CM, Gauldie J, Xing Z.
Source
Department of Pathology and Molecular Medicine & McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Abstract
Lung immunopathology is the main cause of influenza-mediated morbidity and death, and much of its molecular mechanisms remain unclear. Whereas tumor necrosis factor-α (TNF-α) is traditionally considered a proinflammatory cytokine, its role in influenza immunopathology is unresolved. We have investigated this issue by using a model of acute H1N1 influenza infection established in wild-type and TNF-α-deficient mice and evaluated lung viral clearance, inflammatory responses, and immunopathology. Whereas TNF-α was up-regulated in the lung on influenza infection, it was not required for normal influenza viral clearance. However, TNF-α deficiency led, not only to a greater extent of illness, but also to heightened lung immunopathology and tissue remodeling. The severe lung immunopathology was associated with increased inflammatory cell infiltration, anti-influenza adaptive immune responses, and expression of cytokines such as monocyte chemoattractant protein-1 (MCP-1) and fibrotic growth factor, TGF-β1. Thus, in vivo neutralization of MCP-1 markedly attenuated lung immunopathology and blunted TGF-β1 production following influenza infection in these hosts. On the other hand, in vivo transgenic expression of MCP-1 worsened lung immunopathology following influenza infection in wild-type hosts. Thus, TNF-α is dispensable for influenza clearance; however, different from the traditional belief, this cytokine is critically required for negatively regulating the extent of lung immunopathology during acute influenza infection.
Copyright ? 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID:
22001698
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22001698
Negative Regulation of Lung Inflammation and Immunopathology by TNF-α during Acute Influenza Infection.
Damjanovic D, Divangahi M, Kugathasan K, Small CL, Zganiacz A, Brown EG, Hogaboam CM, Gauldie J, Xing Z.
Source
Department of Pathology and Molecular Medicine & McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
Abstract
Lung immunopathology is the main cause of influenza-mediated morbidity and death, and much of its molecular mechanisms remain unclear. Whereas tumor necrosis factor-α (TNF-α) is traditionally considered a proinflammatory cytokine, its role in influenza immunopathology is unresolved. We have investigated this issue by using a model of acute H1N1 influenza infection established in wild-type and TNF-α-deficient mice and evaluated lung viral clearance, inflammatory responses, and immunopathology. Whereas TNF-α was up-regulated in the lung on influenza infection, it was not required for normal influenza viral clearance. However, TNF-α deficiency led, not only to a greater extent of illness, but also to heightened lung immunopathology and tissue remodeling. The severe lung immunopathology was associated with increased inflammatory cell infiltration, anti-influenza adaptive immune responses, and expression of cytokines such as monocyte chemoattractant protein-1 (MCP-1) and fibrotic growth factor, TGF-β1. Thus, in vivo neutralization of MCP-1 markedly attenuated lung immunopathology and blunted TGF-β1 production following influenza infection in these hosts. On the other hand, in vivo transgenic expression of MCP-1 worsened lung immunopathology following influenza infection in wild-type hosts. Thus, TNF-α is dispensable for influenza clearance; however, different from the traditional belief, this cytokine is critically required for negatively regulating the extent of lung immunopathology during acute influenza infection.
Copyright ? 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID:
22001698
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22001698