Monocyte Chemoattractant Protein 1 Contributes to an Adequate Immune Response in Influenza Pneumonia

Clin Immunol. 2007 Dec;125(3):328-36. doi: 10.1016/j.clim.2007.08.001. Epub 2007 Sep 10.

Abstract

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.

MeSH terms

  • Animals
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology*
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL2 / immunology
  • Chemokine CXCL2 / metabolism
  • Flow Cytometry
  • Influenza A virus / immunology*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / metabolism*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / metabolism*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Load

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Chemokine CXCL2
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma