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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Enigmatic inflammasomes.

Kathy Triantafilou1,2

  • 1Immunology Catalyst, Immunology Network, Adaptive Immunity Research Unit, GlaxoSmithKline, Stevenage, UK.

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|February 16, 2021
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Summary
This summary is machine-generated.

Inflammasomes are protein complexes that trigger inflammatory responses and cell death. This review explores lesser-known inflammasomes beyond NLRP3, revealing their diverse roles in immunity and development.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Inflammasomes are cytosolic protein complexes crucial for innate immunity, mediating inflammatory responses and pyroptosis.
  • Activation is a two-step process involving NF-κB-dependent priming (Signal 1) and caspase-1-dependent activation (Signal 2).
  • The NLRP3 inflammasome is well-characterized, but other NLR family members have diverse, often unelucidated functions.

Discussion:

  • This review series focuses on understudied inflammasomes, including NLRP6, NLRP9, NLRX1, NLRC5, and NLRP7.
  • These lesser-known inflammasomes are implicated in non-canonical activation, pathogen restriction, immune regulation, antigen presentation, and sensing bacterial components.
  • Their functions extend beyond typical inflammatory roles, potentially influencing embryonic development.

Key Insights:

  • NLRP3 is the most studied inflammasome, yet numerous other NLR family members possess critical but poorly understood roles.
  • Emerging research highlights diverse functions for inflammasomes like NLRP6, NLRP9, NLRX1, NLRC5, and NLRP7 in immunity and development.
  • The discovery of new inflammasomes and activators underscores the complexity of the NLR field.

Outlook:

  • Further research into lesser-known inflammasomes is essential for a comprehensive understanding of innate immunity.
  • Elucidating the functions of these enigmatic inflammasomes may reveal novel therapeutic targets.
  • Understanding the full NLR family is key to future therapeutic strategies in inflammatory and immune-related diseases.