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How the immune system responds to dying cells can make the difference between an effective homeostatic response and one that provokes or exacerbates pathology. Over the past few years, there have been important advances in our understanding of different forms of cell death — including apoptosis, necrosis, programmed necrosis, necroptosis, pyroptosis, NETosis, immunogenic cell death and activation-induced cell death — and their consequences for immunity. This article series of Nature Reviews Immunology will feature articles that discuss the past progress and latest developments in the intersection between cell death and immunity, in the context of infection, cancer and other settings.
Clearing away dead cells — a process known as efferocytosis — is crucial for normal tissue homeostasis and is impaired in several pathological processes. This Review describes new insights into how efferocytes deal with the engulfed dead cell cargo, how efferocytosis supports the resolution of inflammation and how this understanding is informing new therapeutic strategies.
The gasdermin family of proteins has the capacity to form pores in the membrane, causing a pro-inflammatory lytic type of cell death called pyroptosis, This Review provides a comprehensive overview of the gasdermin family, the mechanisms that control their activation and their role in inflammatory disorders and cancer.
In this Review, Greg Lemke explains how macrophages are able to sense and respond to dead and dying cells. The author discusses the physiological implications of such macrophage activity.
This Review explains how innate sensors of DNA activate different types of programmed cell death. The authors consider the relevance of these cell death pathways during infection and in inflammatory diseases.
In this Timeline article, Shigekazu Nagata and Masato Tanaka highlight some of the key discoveries that have shaped the field of programmed cell death over the past 50 years and explain their relevance for the immune system.
This Review provides an overview of the cross-presentation of antigens derived from dead cells and describes how immunological signals from dying cells influence T cell cross-priming. The authors propose a novel classification of the immunogenic signals that arise from dying cells and discuss how different forms of cell death may influence the outcome of cross-presentation.
This Review describes how different modes of cell death protect against bacterial and viral infections, and the complex signalling crosstalk between the different pathways during an infection.
Initiation of an adaptive immune response depends on the detection of both antigenic epitopes and adjuvant signals. Infectious pathogens and cancer cells often avoid immune detection by limiting the release of danger signals from dying cells. When is cell death immunogenic and what are the pathophysiological implications of this process?