Immunology

Responding with Restraint

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Science  19 Sep 2008:
Vol. 321, Issue 5896, pp. 1606
DOI: 10.1126/science.321.5896.1606b

Eating and breathing are essential activities, but both allow foreign substances and pathogens access to internal epithelial environments—the gut and the lungs. The immune system is poised to launch an effective attack against pathogens in the respiratory tract, yet the response must be limited to avoid collateral damage to airway tissue. Snelgrove et al. report that in mice, this delicate balance is maintained in part by alveolar macrophages in the lower respiratory tract; these cells express a high level of the receptor for CD200, a ligand that coats airway epithelial cells. Binding of CD200 to its receptor inhibits the secretion of inflammatory cytokines. Macrophage receptor expression normally increases during infection of lungs with influenza virus. Mice lacking CD200 showed an increase in alveolar macrophages expressing the cognate receptor, but the resolution of lung inflammation was delayed during a bout of influenza, and these animals eventually died, despite viral clearance from the lungs. Treatment with a soluble form of CD200 did not compromise viral clearance, but limited damaging inflammation. This receptor-ligand pair may be relevant to the search for drugs that dampen inflammation in respiratory conditions, such as asthma and chronic obstructive pulmonary disease, without interfering with responses that control infection. — LC

Nat. Immunol. 9, 1074 (2008).

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