PANoptosis in microbial infection

• Published in: Current opinion in microbiology Vol. 59; pp. 42 - 49
• Main Authors: Place, David E, Lee, SangJoon, Kanneganti, Thirumala-Devi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2021
• Subjects: Apoptosis - immunology; bacteria; Bacterial Physiological Phenomena - immunology; Biological Evolution; Cell Death - physiology; cytokines; evolution; fungi; Fungi - physiology; Host-Pathogen Interactions - immunology; immune system; Infections - immunology; Infections - microbiology; Infections - virology; infectious diseases; inflammation; innate immunity; necroptosis; Necroptosis - immunology; parasites; pathogens; pyroptosis; Pyroptosis - immunology; receptors; Virus Physiological Phenomena - immunology; viruses
• ISSN: 1369-5274; 1879-0364; 1879-0364
• DOI: 10.1016/j.mib.2020.07.012

•Cells exposed to TLR ligands and cytokines during infection activate PANoptosis.•RIPK1-dependent PANoptosome is formed when cell survival signaling is inhibited.•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.