Monocyte chemoattractant protein 1 contributes to an adequate immune response in influenza pneumonia.
Monocyte chemoattractant protein 1 (MCP-1) and its receptor CCR2 have been shown to play an import role in leukocyte recruitment to sites of infection and inflammation. To investigate the role of MCP-1 during infection with influenza we inoculated wild-type (WT) and MCP-1 knockout (KO) mice with a non-lethal dose of a mouse adapted strain of influenza A. Influenza infection of WT mice resulted in a profound increase in pulmonary MCP-1 levels. MCP-1 KO mice had enhanced weight loss and did not fully regain their body weight during the 14-day observation period. In addition, MCP-1 KO mice demonstrated elevated viral loads 8 days after infection, which was accompanied by reduced leukocyte recruitment into the infected lungs, primarily caused by a diminished influx of macrophages and granulocytes. Moreover, pulmonary levels of IgA were reduced in MCP-1 KO mice. The pulmonary concentrations of tumor necrosis factor-alpha, interleukin-6, macrophage inflammatory protein 2 and interferon-gamma were higher in MCP-1 KO mice. This study shows that MCP-1 contributes to an adequate protective immune response against influenza infection in mice.
Dessing
Mark C
MC
Center of Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, The Netherlands. m.c.dessing@amc.uva.nl
van der Sluijs
Koenraad F
KF
Florquin
Sandrine
S
van der Poll
Tom
T
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism*; D011024:Pneumonia, Viral / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D019562:Viral Load