PANoptosis: A New Insight Into Oral Infectious Diseases

Abstract

The oral microbiome, one of the most complex and intensive microbial ecosystems in the human body, comprises bacteria, archaea, fungi, protozoa, and viruses. Dysbiosis of the oral microbiome is the initiating factor that leads to oral infectious diseases. Infection is a sophisticated biological process involving interplay between the pathogen and the host, which often leads to activation of programmed cell death. Studies suggest that pyroptosis, apoptosis, and necroptosis are involved in multiple oral infectious diseases. Further understanding of crosstalk between cell death pathways has led to pyroptosis, apoptosis, and necroptosis being integrated into a single term: PANoptosis. PANoptosis is a multifaceted agent of the immune response that has important pathophysiological relevance to infectious diseases, autoimmunity, and cancer. As such, it plays an important role in innate immune cells that detect and eliminate intracellular pathogens. In addition to the classical model of influenza virus-infected and Yersinia-infected macrophages, other studies have expanded the scope of PANoptosis to include other microorganisms, as well as potential roles in cell types other than macrophages. In this review, we will summarize the pathophysiological mechanisms underlying inflammation and tissue destruction caused by oral pathogens. We present an overview of different pathogens that may induce activation of PANoptosis, along with the functional consequences of PANoptosis in the context of oral infectious diseases. To advance our understanding of immunology, we also explore the strategies used by microbes that enable immune evasion and replication within host cells. Improved understanding of the interplay between the host and pathogen through PANoptosis will direct development of therapeutic strategies that target oral infectious diseases.

Enterococcus faecalis -Induced Macrophage Necroptosis Promotes Refractory Apical Periodontitis

“…With the release of death-associated molecular patterns, necroptotic cells can transmit danger signals and activate inflammatory responses. Macrophages are important mediators of host inflammatory responses to infection ( 20 ). In the current study, we found abundant macrophage infiltration in periapical lesion specimens from RAP-diagnosed patients as well as from an experimental RAP model.…”

“…PANoptosis, a newly emerging concept highlighting the cross talk and coordination between pyroptosis, apoptosis, and necroptosis, has been proposed ( 34 ). Recently, we have reviewed the functional consequences and activation mechanisms of PANoptosis in oral infectious diseases ( 20 ). E. faecalis infection can induce pyroptosis, apoptosis, and necroptosis of macrophages based on previous and current studies ( 18 , 35 , 36 ).…”

Talaromyces marneffei activates the AIM2-caspase-1/-4-GSDMD axis to induce pyroptosis in hepatocytes

“…Apoptosis has been the subject of intensive research in the past three decades while pyroptosis has become ahot trend in recent years. Therefore, with the concept of pan-apoptosis (PANoptosis), the research prospect of necroptosis is foreseeable as the last link of the triangle relationship [ 57 , 58 ]. PANoptosis is amultifaceted immune response with important pathophysiological implications for infectious diseases, autoimmunity, and cancer, reflecting the complexity of host responses to pathogens and the interconnectedness of signaling pathways.…”

Intestinal Gasdermins for regulation of inflammation and tumorigenesis

“…PANoptosis is modulated by the multi-protein PANoptosome complex, which provides a molecular scaffold for simultaneous engagement of key molecules from pyroptosis, apoptosis and necroptosis (107). According to the biological functions, compositions of the PANoptosome consist of sensors, adaptors and catalytic effectors in general, such as Z-DNA binding protein 1 (ZBP1), FADD and caspase-1, respectively (108). Since PANoptosis has been triggered during various pathogenic infections, autoinflammatory diseases and cancer (107), indicating that it has significant pathophysiological relevance.…”