A critical function for CD200 in lung immune homeostasis and the severity of influenza infection

Robert J Snelgrove, et al. 2008. Nature Immunology. 9, 1074 - 1083

Speaker: Yi Chun Chen (陳逸純)                           Time: 15:00~16:00, Sep 24, 2008

Commentator: Dr. Pin Ling (凌斌教授)          Place: Room 601

Abstract:

Lung alveolar macrophages exist in an environment of abundant antigenic material, most of which must be ignored except when the antigen represents a serious threat. The authors demonstrated here that airway macrophages had higher expression of the negative regulator CD200 receptor (CD200R) than did their systemic counterparts and they supposed that CD200 might play a role in lung immune suppress. Therefore they incubated lung macrophages  with airway epithelial cell which can present CD200, found that macrophages could be restrained by epithelial cell. And, they identified some CD200^-/- macrophage, and treated with LPS and IFN-γ to initiate imflammatory. After that they detected higher level expressions of MHC class II and inflammatory cytokines. In aniaml model, they also found that mice lacking CD200 were sensitive to influenza infection and induced serious inflammation. The infected CD200 knockout mice had enhanced macrophage activities and released kinds of inflammatory cytokines such as IL-6 and TNF. Although the virus titer would be reduced, mice lacking of CD200 would cause more serious inflammation and, ultimately, death. To confirm the relationship between CD200 and influenza infection, the influenza-infected CD200^-/- mice were received fusion proteins of CD200 and the Fc region or the OX110 agonistic monoclonal antibody to CD200R. They found mice treated with fusion proteins and OX110 antibody reduced weight loss and inflammation than treated with  isotype control antibody. In conclusion, the authors deemed that the administration of agonists that bind CD200R 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.

References:

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2.      Wright, G.J. et al. 2003. Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. J. Immunol. 171, 3034–3046.