Pyroptotic cell death defends against intracellular pathogens

Jørgensen, Ine; Miao, Edward A.

doi:10.1111/imr.12287

Cited by 868 publications

(697 citation statements)

References 128 publications

(193 reference statements)

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“…AIM2 senses DNA and forms a heterocomplex with the adaptor protein apoptosis-associated speck-like protein (ASC). Formation of the functional inflammasome complex activates caspase-1 that in turn acts to generate matured forms of IL-1β and IL-18 [79], and causes a type of cell death called pyroptosis [80]. APCs that are deficient in the AIM2 inflammasome show marked overactivation of the STING pathway [81], indicating that induction of pyroptosis by the AIM2 inflammsome normally acts to dampen STING pathway activation.…”

Section: Potential Role For Additional Innate Immune Sensorsmentioning

confidence: 99%

Innate immune signaling and regulation in cancer immunotherapy

et al. 2016

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A pre-existing T cell-inflamed tumor microenvironment has prognostic utility and also can be predictive for response to contemporary cancer immunotherapies. The generation of a spontaneous T cell response against tumor-associated antigens depends on innate immune activation, which drives type I interferon (IFN) production. Recent work has revealed a major role for the STING pathway of cytosolic DNA sensing in this process. This cascade of events contributes to the activation of Batf3-lineage dendritic cells (DCs), which appear to be central to anti-tumor immunity. Non-T cell-inflamed tumors lack chemokines for Batf3 DC recruitment, have few Batf3 DCs, and lack a type I IFN gene signature, suggesting that failed innate immune activation may be the ultimate cause for lack of spontaneous T cell activation and accumulation. With this information in hand, new strategies for triggering innate immune activation and Batf3 DC recruitment are being developed, including novel STING agonists for de novo immune priming. Ultimately, the successful development of effective innate immune activators should expand the fraction of patients that can respond to immunotherapies, such as with checkpoint blockade antibodies.

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Section: Potential Role For Additional Innate Immune Sensorsmentioning

confidence: 99%

Innate immune signaling and regulation in cancer immunotherapy

et al. 2016

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“…The term pyroptosis comes from the Greek words 'pyro', which means fire (denoting the release of proinflammatory mediators) and 'ptosis', which means falling, a term commonly used to describe cell death [110]. Pyroptosis is initiated by caspase-1 following its activation by diverse inflammasomes, resulting in the lysis of infected cells.…”

Section: Regulation Of Inflammasome Activity and Il-1b Secretion Pyromentioning

confidence: 99%

“…The activation of inflammatory caspases results in the formation of pores in the plasmatic membrane that measure approximately 1.1-2.4 lm in diameter, leading to an increase in cellular permeability [111]. Thus, the features of pyroptosis include rapid plasma membrane rupture and the release of intracellular proinflammatory contents such as DAMPs and cytokines, which induce a robust inflammatory response [110]. Destruction of the actin cytoskeleton has also been observed in pyroptotic cells, but the mechanism and importance of this event remain unclear [18,112,113].…”

Section: Regulation Of Inflammasome Activity and Il-1b Secretion Pyromentioning

confidence: 99%

Inflammasomes and its importance in viral infections

León-Juárez²,

et al. 2016

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A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1. The inflammasome operates as a platform for caspase-1 activation, resulting in caspase-1-dependent proteolytic maturation and secretion of interleukin (IL)-1b and IL-18. This, in turn, activates the expression of other immune genes and facilitates lymphocyte recruitment to the site of primary infection, thereby controlling invading pathogens. Moreover, inflammasomes counter viral replication and remove infected immune cells through an inflammatory cell death, program termed as pyroptosis. As a countermeasure, viral pathogens have evolved virulence factors to antagonise inflammasome pathways. In this review, we discuss the role of inflammasomes in sensing viral infection as well as the evasion strategies that viruses have developed to evade inflammasome-dependent immune responses. This information summarises our understanding of host defence mechanisms against viruses and highlights research areas that can provide new approaches to interfere in the pathogenesis of viral diseases.

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“…Pyroptosis, distinct both morphologically and molecularly from apoptosis, occurs following the activation of inflammatory caspases and cleavage of gasdermin D, which induces membrane rupture and the leakage of cytosolic contents, thereby damaging the replication niche of intracellular pathogens and rendering them vulnerable to neutrophils. 23,24 Pyrin domainharboring NLRP3 and AIM2 inflammasomes signal exclusively through the ASC (apoptosis-associated speck-like protein containing a CARD) adaptor to recruit and activate caspase-1. By contrast, the CARD domain-harboring NLRC4 inflammasome can signal to caspase-1 directly to elicit pyroptosis and indirectly through the adaptor ASC to augment IL-1β and IL-18 secretion.…”

Section: Inflammasome Signalingmentioning

confidence: 99%

The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

Chai

Liu

2016

Cell Mol Immunol

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The ubiquitin system comprises enzymes that are responsible for ubiquitination and deubiquitination, as well as ubiquitin receptors that are capable of recognizing and deciphering the ubiquitin code, which act in coordination to regulate almost all host cellular processes, including host-pathogen interactions. In response to pathogen infection, the host innate immune system launches an array of distinct antimicrobial activities encompassing inflammatory signaling, phagosomal maturation, autophagy and apoptosis, all of which are fine-tuned by the ubiquitin system to eradicate the invading pathogens and to reduce concomitant host damage. By contrast, pathogens have evolved a cohort of exquisite strategies to evade host innate immunity by usurping the ubiquitin system for their own benefits. Here, we present recent advances regarding the ubiquitin system-mediated modulation of host-pathogen interplay, with a specific focus on host innate immune defenses and bacterial pathogen immune evasion.

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Pyroptotic cell death defends against intracellular pathogens

Cited by 868 publications

References 128 publications

Innate immune signaling and regulation in cancer immunotherapy

Innate immune signaling and regulation in cancer immunotherapy

Inflammasomes and its importance in viral infections

The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

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