Immunogenic and tolerogenic cell death

How should the immune system respond to a dying cell? Should it ignore it (to allow normal tissue turnover), tolerate it (to prevent autoimmunity) or respond to it (to clear pathogens or tumours)? This Review describes our current understanding of the mechanisms involved in this decision. The immune system is routinely exposed to dead cells during normal cell turnover, injury and infection. Mechanisms must exist to discriminate between different forms of cell death to correctly eliminate pathogens and promote healing while avoiding responses to self, which can result in autoimmunity. However, an effective immune response against host tissue is often needed to eliminate tumours following treatment with chemotherapeutic agents that trigger tumour cell death. Consequently, a central problem in immunology is to understand how the immune system determines whether cell death is immunogenic, tolerogenic or 'silent'.