Immunol Rev. 9. PDF - AIM2, a cytosolic DNA sensor, plays an important role during infection caused by pathogens with double-stranded DNA; however, its role in human cytomegalovirus (HCMV) infection remains unclear. The AIM2 inflammasome: Sensor of pathogens and cellular perturbations. Sensor of pathogens and cellular perturbations. 11. For these reasons, macrophages are often . Crossref Provided original full text link. Download PDF: Sorry, we are unable to provide the full text but you may find it at the following location(s): https://api.wiley.com/onlineli. AIM2 is a cytosolic innate immune receptor which recognizes doublestranded DNA (dsDNA) released during cellular perturbation and pathogenic assault. Research over the past decade has revealed that AIM2 plays essential roles not only in host defense against pathogens but also in inflammatory diseases, autoimmunity, and cancer in inflammasomedependent and inflammaomeindependent manners. Potassium efflux, mitochondria dysfunction, and lysosomal disruption have been reported to mediate the activation of NLRP3, leading to the hypothesis that this inflammasome is a guardian of cellular integrity (11, 12).In addition to detecting mitochondrial perturbations, NLRP3 was found to be activated by . AIM2 (absent in melanoma 2) is a cytoplasmic sensor of double-stranded DNA from pathogens or damaged cellular organelles. 2018;281(1):99-114 46. It recruits ASC (apoptosis-associated specklike protein containing a CARD) and caspase-1 to form the AIM2 inflammasome, activate caspase-1, and elicit inflammatory responses via cytokine maturation and pyroptotic cell death. Despite exhibiting enhanced caspase-1-dependent cell death following inflammasome activation (Figure 2K), Lrrk2 G2019S BMDMs release markedly less IL-1 post-AIM2 stimulation and at 24 h post-Mtb infection (Figure 2S). AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. When HIN domain senses damaged-associated molecular patterns (DAMPs), AIM2 recruited apoptosis speck-like protein (ASC) and caspase-1 to form a molecular platform for the maturation and secretion of IL-1 and IL-18 ( de Rivero Vaccari et al., 2014 ). Dick M S, Sborgi L, Ruhl S. et al. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. Several distinct inflammasomes have been identified, each differentiated by unique activators, NLR/ALR family members, and caspase effectors. Recent studies have demonstrated that AIM2 detects self-DNA. Nature immunology.2009;10:266- 272. Abstract Abstract is not available. Survival of temporal cortical neurons after SAH was assessed by Nissl staining. 12 an inflammasomeindependent pathway of aim2 has also been discovered, controlling Previously, we showed an increase in AIM2 protein levels during the early stage of HCMV infection and a decrease 24 h post infection. to AIM2 oligomerization and the recruitment of the adaptor ASC and the protease caspase-1 to the forming inflammasome (7-10). This study was aimed to investigate the role of mitochondrial DNA synthesis-induced activation of Absent in melanoma 2 (AIM2) inflammasome and pyroptosis in NAFLD. It recruits ASC (apoptosis-associated specklike protein containing a CARD) and caspase-1 to form the AIM2 inflammasome, activate caspase-1, and elicit inflammatory responses via cytokine maturation and pyroptotic . behaves as a guardian of cellular integrity that can responds to perturbations and loss of cellular homeostasis such as, for example, disruption of nuclear envelope integrity. All four pathogens activate the canonical caspase-1-dependent NLRP3 inflammasome by inducing ROS, K + efflux, and . AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. Cell death by pyroptosis inhibits the ISD pathway and the production of IL-10 Full size image The negative regulation of type I IFN response by Aim2/AIM2 proteins AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. Macrophages are immune cells that are important for the development of the defensive front line of the innate immune system. Nat Commun. Four inflammasome complexes are activated when engaged by systemic fungal pathogens. Caspases. AIM2 (absent in melanoma 2) is a cytoplasmic sensor of double-stranded DNA from pathogens or damaged cellular organelles. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment Upon stimulation, the inflammasomes activate the production of the pro-inflammatory cytokines IL-1 and IL-18 and induce gasdermin D-mediated pyroptosis. The majority of the neurons with large cell bodies and . 2016;7:11929 47. CAS PubMed Google Scholar (external link) Recent studies have shown that the detection of self-DNA species by AIM2 is an important factor that contributes to diseases associated with perturbation of cellular homeostasis. However, AIM2 achieves specificity by detecting . AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. When cytoplasmic dsDNA is detected by AIM2, the AIM2 inflammasome is formed; this leads to the release of the proinflammatory cytokines, IL-1 and IL-18, and the induction of pyroptosis. Jrme Lugrin; Fabio Martinon; Publication date 2017. Full text. This study investigated the role of the absent in melanoma 2 (AIM2) inflammasome as a DNA damage sensor in nucleus pulposus (NP) cells. One of these mechanisms is the targeting of members of the IFN regulatory factor family. However, how this detection is regulated to achieve specificity in order to detect pathogen and . Candida, Aspergillus, Cryptococcus, and Paracoccidioides trigger priming-associated receptors (e.g., dectin-1 and TLR2), thereby promoting the first step (priming) of inflammasome activation. This raises several questions that remain to be elucidated. Pyroptosis is a newly characterized type of programmed cell death. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. AIM2 inflammasome is activated by cytosolic dsDNA from host and pathogens through its binding to C-terminal HIN domain of AIM2 (5, 6). Methods. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. At least 14 cytoplasmic DNA sensors have been identified in recent years, each with specialized roles in driving inflammation and/or cell death. We found that the level of AIM2 increased in degenerated discs and was correlated to the degree of IDD. 2 1 INTRODUCTION . journal-article; Similar works. Background AIM2, a cytosolic DNA sensor, plays an important role during infection caused by pathogens with double-stranded DNA; however, its role in human cytomegalovirus (HCMV) infection remains unclear. biochemical studies have demonstrated that aim2 can directly bind dna, and there are three major features of the aim2-dna interaction ( 19 ): ( 1) the interaction is hin domain-dependent, as hin domain has two oligonucleotide/oligosaccharide binding folds that have high affinity to dna; ( 2) it is independent of dna sequence, gc content, or 10. Mice were raised on a high-fat diet for 24 wk to establish NAFLD models. Publisher Wiley. Recently, mounting evidence has linked the AIM2 inflammasome-IL-1 pathway to the pathogenesis of psoriasis. These responses use a set of germline-encoded pattern recognition . As another canonical readout of AIM2 inflammasome activation, we measured IL-1 release in WT and Lrrk2 G2019S BMDMs. Potassium efflux, mitochondria dysfunction, and ly-sosomal disruption have been reported to mediate the activation of AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. Of these, AIM2 is a sensor of dsDNA, and forms an inflammasome complex to activate the cysteine protease caspase-1, mediates the release of the proinflammatory cytokines IL-1 and IL-18, and . Burckstummer T, et al. Last time updated on 12/11/2019. Besides the physiologic role mediated by inflammasome in the maintenance of homeostasis and in the first-line pathogen defense, the complex hyper-activation or dysregulation has been implicated in the pathogenesis of several human conditions Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. Pathogens such as HIV-1 that cause chronic infections are particularly capable at adapting to the host in a manner that ensures long-term residence, and have evolved numerous mechanisms to evade various aspects of the innate and adaptive immune response. Download Citation | On Oct 17, 2022, Nagakannan Pandian and others published PANoptosis: A Unique Innate Immune Inflammatory Cell Death Modality | Find, read and cite all the research you need on . Thus, in addition of being a sensor of pathogen associated molecular patterns (PAMPs), the AIM2 inflammasome is emerging as a key guardian of cellular integrity. Here, we extensively and systematically compiled genes associated with pyroptosis, integrated multiomics data and clinical data across 31 cancer types from The Cancer Genome Atlas, and delineated the global alterations in PRGs at . Previously, we showed an increase in AIM2 protein levels during the early stage of HCMV infection and a decrease 24 h post infection. Morrone S R, Matyszewski M, Yu X. et al. However AIM2 achieve specificity by detecting altered or misslocalized DNA molecules. Serum AIM2 levels among health controls (HC, ), OA ( ), and RA ( n =49) patients were compared via ELISA. The term inflammasome was introduced by Martinon et al., in 2002 to describe an intracellular high-molecular-weight complex that mediates the activation of inflammatory caspases ().Inflammasomes are multimeric protein complexes, known as first responders in the innate immune response, sensing a wide spectrum of pathogens (pathogen-associated molecular patterns), stress, and . To determine differences in AIM2 inflammasome expression levels between rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate the role of AIM2 in RA fibroblast-like synoviocytes (RA-FLS). AIM2 recognition of dsDNA leads to the. Because HCMV has developed a variety of strategies to . The activation of the Aim2 inflammasome and pyroptosis contributes to AD-related inflammation and associated neurotoxicity, resulting in neurodegeneration. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. Of these, AIM2 is a sensor of dsDNA, and forms an inflammasome complex to activate the cysteine protease caspase-1, mediates the release of the proinflammatory cytokines IL-1 and IL-18, and induces . Thus, in addition of being a sensor of pathogen associated molecular patterns (PAMPs), the AIM2 inflammasome is emerging as a key guardian of cellular integrity. However, its function in cancer progression and its response to treatments remain controversial. Following signal recognition, macrophages undergo activation toward specific functional states, consisting not only in the acquisition of specific features but also of peculiar metabolic programs associated with each function. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. Abstract. Mentioning: 114 - Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. This inflammasome assembly leads to the secretion of bioactive interleukin-1 (IL-1) and IL-18 and induction of an inflammatory . Failure of the inflammasomes to rapidly clear the insults or restore tissue homeostasis can result in chronic inflammation. Inflammasomes are multiprotein complexes capable of sensing pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and cellular perturbations. AIM2, a protein encoded by the AIM2 gene in humans, is an integral component of the immune system. The AIM2 inflammasome: Sensor of pathogens and cellular perturbations[J]. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. 1 recent developments have indicated that aim2 contributes to the tumorigenesis of nonsmallcell lung cancer (nsclc) via regulation of mitochondrial dynamics and inflammasome activation. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Activators of the NLRP3 inflammasome are heterogeneous, ranging from self-originating uric acid, calcium pyrophosphate crystals, cholesterol crystals, ATP and glucose to environment-derived alum, silica and . Because HCMV has developed a variety of strategies to evade . Nucleic acid sensing is a critical mechanism by which the immune system monitors for pathogen invasion. AIM2 is a cytosolic innate immune receptor which recognizes double-stranded DNA (dsDNA) released during cellular perturbation and pathogenic assault. Related questions. ASC filament formation serves as a signal amplification mechanism for inflammasomes[J]. 2018;281:99-114. . AIM2 recognition of dsDNA leads to the assembly of a large multiprotein oligomeric complex termed the inflammasome. Introduction. F4/80 immunofluorescence was performed to reflect the inflammatory response in the liver of mice. AIM2 inflammasome-mediated pyroptosis in the temporal cortex. The classical or canonical inflammasome complex consists of a cytosolic sensor (which can be either a nucleotide-binding domain and leucine-rich-repeat-containing [NLR] protein or an AIM2-like receptor [ALR] protein), an adaptor protein (apoptosis . Authors. The AIM2 inflammasome: Sensor of pathogens and cellular perturbations J. Lugrin, F. Martinon Published 1 January 2018 Biology Immunological Reviews Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and. Pathogens as well as signals triggered by cellular perturbations engage innate immune programs. aim2 was originally described as a tumor suppressor for melanoma. Nature.2009;458:509- 513. The AIM2 inflammasome: sensor of pathogens and cellular perturbations. Page Martinon Fabio of site Department of Immunobiology hosted by the University of Lausanne AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. Immunol Rev. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. Other inflammasomes have been shown to detect intrinsic cellular perturbations. AIM2 inflammasome is a large multi-protein caspase-2 activating complex formed by AIM2 protein and the adaptor ASC. The inflammasomes are intracellular protein complexes that are assembled in response to a variety of perturbations including infections and injuries. Other inflammasomes have been shown to detect intrinsic cellular perturbations.
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