Macrophage-inducible C-type lectin (Mincle) is expressed mainly in macrophages and is induced after exposure to various stimuli and stresses. Here we show that Mincle selectively associated with the Fc receptor common gamma-chain and activated macrophages to produce inflammatory cytokines and chemokines. Mincle-expressing cells were activated in the presence of dead cells, and we identified SAP130, a component of small nuclear ribonucloprotein, as a Mincle ligand that is released from dead cells. To investigate whether Mincle is required for normal responses to cell death in vivo, we induced thymocyte death by irradiating mice and found that transient infiltration of neutrophils into the thymus could be blocked by injection of Mincle-specific antibody. Our results suggest that Mincle is a receptor that senses nonhomeostatic cell death and thereby induces the production of inflammatory cytokines to drive the infiltration of neutrophils into damaged tissue.