Debating DAP12

Mice that lack the adaptor protein DAP12 defy deadly bacterial infections, according to Turnbull and colleagues on page 363. DAP12-deficient mice developed a muted inflammatory response, allowing the immune system to clear the bacteria without triggering septic shock.

DAP12 is a transmembrane adaptor protein that is associated with an array of activating receptors on the surface of immune, brain, and bone cells. DAP12 is required for the development of bone-resorbing osteoclasts, but its role in immune cells is less clear. Some studies have suggested that DAP12-dependent signals amplify cellular activation and inflammatory cytokine production in response to invading microbes, but others argue that DAP12 signaling inhibits these functions.

Turnbull et al. now weigh in on this debate by showing that mice lacking DAP12 can fend off a systemic bacterial infection without producing shock-inducing...