Immunosuppression and ensuing infections, especially aspiration pneumonia, commonly occur after ischemic brain infarcts and contribute substantially to the mortality that can follow a stroke. In Science, Kubes and colleagues identify a neural circuit that connects brain ischemia to alterations in the function of hepatic invariant natural killer T cell (iNKT cells) that lead to the suppression of adaptive immune responses. In a mouse model of stroke, liver iNKT cells alter their migration and switch from producing interferon-g and interleukin 12 to producing interleukin 10. Surprisingly, these changes do not require presentation of glycolipids mediated by the antigen-presenting molecule CD1d but instead are induced by neutrotransmitters, as blocking b-adrenergic receptors reverses these effects. Likewise, mice treated with neuroinhibitors fail to become immunosuppressed in the stroke model. Administration of the iNKT cell agonist a-GalCer likewise reverses the immunosuppression. These findings highlight an intriguing connection between neural circuits activated by brain infarcts and iNKT cells.

Science (15 September 2011) doi:10.1126/science.1210301