tetano
Editor, Senior Moderator
J Virol. 2010 May 26. [Epub ahead of print]
The Critical Role of Airway Macrophages in Modulating Disease Severity During Influenza Virus Infection of Mice.
Tate MD, Pickett DL, van Rooijen N, Brooks AG, Reading PC.
Department of Microbiology and Immunology, University of Melbourne, Parkville, 3010, Victoria, Australia; Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit of Amsterdam, Amsterdam, The Netherlands; WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, 3051, Victoria, Australia.
Abstract
Airway macrophages provide a first line of host defence against a range of airborne pathogens, including influenza virus. In this study we show that influenza viruses differ markedly in their ability to infect murine macrophages in vitro and that infection of macrophages is non-productive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways leading to severe airway inflammation, pulmonary edema and vascular leak, indicative of lung injury. Thymic atrophy, lymphopenia and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice.
PMID: 20504924 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20504924
The Critical Role of Airway Macrophages in Modulating Disease Severity During Influenza Virus Infection of Mice.
Tate MD, Pickett DL, van Rooijen N, Brooks AG, Reading PC.
Department of Microbiology and Immunology, University of Melbourne, Parkville, 3010, Victoria, Australia; Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit of Amsterdam, Amsterdam, The Netherlands; WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, 3051, Victoria, Australia.
Abstract
Airway macrophages provide a first line of host defence against a range of airborne pathogens, including influenza virus. In this study we show that influenza viruses differ markedly in their ability to infect murine macrophages in vitro and that infection of macrophages is non-productive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways leading to severe airway inflammation, pulmonary edema and vascular leak, indicative of lung injury. Thymic atrophy, lymphopenia and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice.
PMID: 20504924 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20504924