The Antisocial Network: Cross Talk Between Cell Death Programs in Host Defense
Annelise G Snyder1, Andrew Oberst2
1NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Abstract:
Nearly all animal cells contain proteins evolved to trigger the destruction of the cell in which they reside. The activation of these proteins occurs via sequential programs, and much effort has been expended in delineating the molecular mechanisms underlying the resulting processes of programmed cell death (PCD). These efforts have led to the definition of apoptosis as a form of nonimmunogenic PCD that is required for normal development and tissue homeostasis, and of pyroptosis and necroptosis as forms of PCD initiated by pathogen infection that are associated with inflammation and immune activation. While this paradigm has served the field well, numerous recent studies have highlighted cross talk between these programs, challenging the idea that apoptosis, pyroptosis, and necroptosis are linear pathways with defined immunological outputs. Here, we discuss the emerging idea of cell death as a signaling network, considering connections between cell death pathways both as we observe them now and in their evolutionary origins. We also discuss the engagement and subversion of cell death pathways by pathogens, as well as the key immunological outcomes of these processes.
Insights
Programmed cell death (PCD) pathways like apoptosis, pyroptosis, and necroptosis are interconnected. Emerging research reveals cell death as a complex signaling network, not linear pathways, with significant immunological implications.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Animal cells possess proteins that initiate programmed cell death (PCD).
- Apoptosis, pyroptosis, and necroptosis are distinct PCD forms with varying immunological outcomes.
- Traditional views considered these pathways linear and immunologically defined.
Purpose of the Study:
- To discuss cell death as an integrated signaling network.
- To explore the cross-talk and evolutionary origins of cell death pathways.
- To examine pathogen interactions with cell death mechanisms and their immunological consequences.
Main Methods:
- Review and synthesis of recent studies on programmed cell death.
- Analysis of molecular mechanisms underlying apoptosis, pyroptosis, and necroptosis.
- Investigation of evolutionary connections and pathogen subversion of cell death pathways.
Main Results:
- Recent findings challenge the linear model of PCD pathways.
- Significant cross-talk exists between apoptosis, pyroptosis, and necroptosis.
- Cell death pathways are increasingly viewed as a complex signaling network.
Conclusions:
- Programmed cell death operates as a dynamic signaling network rather than discrete pathways.
- Understanding these interconnected pathways is crucial for comprehending development, homeostasis, and immune responses.
- Pathogen manipulation of cell death pathways highlights their central role in host-pathogen interactions and inflammation.
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