A Critical Function for CD200 in Lung Immune Homeostasis and the Severity of Influenza Infection

Nat Immunol. 2008 Sep;9(9):1074-83. doi: 10.1038/ni.1637. Epub 2008 Jul 27.

Abstract

The lung must maintain a high threshold of immune 'ignorance' to innocuous antigens to avoid inflammatory disease that depends on the balance of positive inflammatory signals and repressor pathways. We demonstrate here that airway macrophages had higher expression of the negative regulator CD200 receptor (CD200R) than did their systemic counterparts. Lung macrophages were restrained by CD200 expressed on airway epithelium. Mice lacking CD200 had more macrophage activity and enhanced sensitivity to influenza infection, which led to delayed resolution of inflammation and, ultimately, death. The administration of agonists that bind CD200R, however, prevented inflammatory lung disease. Thus, CD200R is critical for lung macrophage immune homeostasis in the resting state and limits inflammatory amplitude and duration during pulmonary influenza infection.

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • Cytokines / biosynthesis
  • Homeostasis / immunology
  • Homeostasis / physiology*
  • Humans
  • Influenza, Human / immunology*
  • Influenza, Human / pathology
  • Lung / immunology*
  • Lung / metabolism
  • Mice
  • Myeloid Cells / immunology*

Substances

  • Antigens, CD
  • Cytokines
  • antigens, CD200