CCR2+ Monocyte-Derived Dendritic Cells and Exudate Macrophages Produce Influenza-Induced Pulmonary Immune Pathology and Mortality
Top Cited Papers
- 15 February 2008
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 180 (4), 2562-2572
- https://doi.org/10.4049/jimmunol.180.4.2562
Abstract
Infection with pathogenic influenza virus induces severe pulmonary immune pathology, but the specific cell types that cause this have not been determined. We characterized inflammatory cell types in mice that overexpress MCP-1 (CCL2) in the lungs, then examined those cells during influenza infection of wild-type (WT) mice. Lungs of both naive surfactant protein C-MCP mice and influenza-infected WT mice contain increased numbers of CCR2+ monocytes, monocyte-derived DC (moDC), and exudate macrophages (exMACs). Adoptively transferred Gr-1+ monocytes give rise to both moDC and exMACs in influenza-infected lungs. MoDC, the most common inflammatory cell type in infected lungs, induce robust naive T cell proliferation and produce NO synthase 2 (NOS2), whereas exMACs produce high levels of TNF-α and NOS2 and stimulate the proliferation of memory T cells. Relative to WT mice, influenza-infected CCR2-deficient mice display marked reductions in the accumulation of monocyte-derived inflammatory cells, cells producing NOS2, the expression of costimulatory molecules, markers of lung injury, weight loss, and mortality. We conclude that CCR2+ monocyte-derived cells are the predominant cause of immune pathology during influenza infection and that such pathology is markedly abrogated in the absence of CCR2.Keywords
This publication has 53 references indexed in Scilit:
- Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sitesJCI Insight, 2007
- Chemokine regulation of the inflammatory response to a low-dose influenza infection in CCR2–/– miceJournal of Leukocyte Biology, 2006
- Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient miceJournal of General Virology, 2006
- The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophagesBlood, 2006
- Influenza and the challenge for immunologyNature Immunology, 2006
- Monocyte and macrophage heterogeneityNature Reviews Immunology, 2005
- Avian Influenza A (H5N1) Infection in HumansNew England Journal of Medicine, 2005
- Influenza A H5N1 Replication Sites in HumansEmerging Infectious Diseases, 2005
- Human Disease from Influenza A (H5N1), Thailand, 2004Emerging Infectious Diseases, 2005
- CCR2-positive monocytes recruited to inflamed lungs downregulate local CCL2 chemokine levelsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005