Cells exposed to TLR ligands and cytokines during infection activate PANoptosis.
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RIPK1-dependent PANoptosome is formed when cell survival signaling is inhibited.
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Influenza A virus Z-RNAs bind and activate ZBP1, promoting PANoptosome formation.
The immune system has evolved multiple mechanisms to restrict microbial infections and regulate inflammatory responses. Without appropriate regulation, infection-induced inflammatory pathology can be deadly. The innate immune system recognizes the microbial molecules conserved in many pathogens and engages a rapid response by producing inflammatory mediators and activating programmed cell death pathways, including pyroptosis, apoptosis, and necroptosis. Activation of pattern recognition receptors, in combination with inflammatory cytokine-induced signaling through death domain-containing receptors, initiates a highly interconnected cell death process called PANoptosis (pyroptosis, apoptosis, necroptosis). Broadly speaking, PANoptosis is critical for restricting a wide range of pathogens (including bacteria, viruses, fungi, and parasites), which we describe in this review. We propose that re-examining the role of cell death and inflammatory cytokines through the lens of PANoptosis will advance our understanding of host–pathogen evolution and may reveal new treatment strategies for controlling a wide range of infectious diseases.
Given her role as Guest Editor, Thirumala-Devi Kanneganti had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Wolf-Dietrich Hardt.
