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https://www.readbyqxmd.com/read/28683296/inflammasomes-on-the-crossroads-of-innate-immune-recognition-and-metabolic-control
#1
REVIEW
Tomasz Próchnicki, Eicke Latz
Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. The signals activating other inflammasomes, NLRP3, NLRP6, and pyrin, are less well understood. Recent studies implicated several low-molecular-weight compounds traditionally linked to metabolism, not immunity, in modulation of inflammasome signaling...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28679751/aim2-like-receptors-positively-and-negatively-regulate-the-interferon-response-induced-by-cytosolic-dna
#2
Yuki Nakaya, Jingtao Lilue, Spyridon Stavrou, Eileen A Moran, Susan R Ross
Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melanoma 2 (AIM2)-like receptors (ALRs) have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production...
July 5, 2017: MBio
https://www.readbyqxmd.com/read/28663562/expression-analysis-of-inflammasome-sensors-and-implication-of-nlrp12-inflammasome-in-prostate-cancer
#3
Dev Karan, Ossama Tawfik, Seema Dubey
Inflammasomes are multi-proteins complex regulating inflammation-associated signaling. While inflammation plays a critical role in cancer cell growth, studies remain uncharacterized on the role of inflammasomes in prostate cancer. Using Gene Expression Omnibus (GEO) public datasets, we screened the expression profiles of inflammasome sensors NLRP3, NLRC4, NLRP6, NRLP12, and AIM2 in prostate tumor tissues, and verified their mRNA level in a panel of prostate cancer cell lines. The selected expression of NLRP3 and NLRP12 inflammasomes was validated, and the clinical association was evaluated in human prostate archival tumor tissues...
June 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642849/aim2-co-immunization-with-vp1-is-associated-with-increased-memory-cd8-t-cells-and-mounts-long-lasting-protection-against-coxsackievirus-b3-challenge
#4
Liang Yin, Dafei Chai, Yan Yue, Chunsheng Dong, Sidong Xiong
The recurrent Coxsackievirus B3 (CVB3) infection is the most important cause of intractable myocarditis which often leads to chronic myocarditis and even dilated cardiomyopathy. Therefore, enhanced DNA vaccines capable of memory CD8 T cells are essential for long-lasting immunological protection against CVB3 infection. In this study, absent in melanoma 2 (AIM2) was used as an adjuvant to enhance the induction of memory CD8 T cells elicited by VP1 (viral capsid protein 1) vaccine. Mice were intramuscularly injected with 50 μg AIM2 plasmid and equal amount of VP1 plasmid (pAIM2/pVP1) vaccine 4 times at 2 week-intervals...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28621333/francisella-requires-dynamic-type-vi-secretion-system-and-clpb-to-deliver-effectors-for-phagosomal-escape
#5
Maj Brodmann, Roland F Dreier, Petr Broz, Marek Basler
Francisella tularensis is an intracellular pathogen that causes the fatal zoonotic disease tularaemia. Critical for its pathogenesis is the ability of the phagocytosed bacteria to escape into the cell cytosol. For this, the bacteria use a non-canonical type VI secretion system (T6SS) encoded on the Francisella pathogenicity island (FPI). Here we show that in F. novicida T6SS assembly initiates at the bacterial poles both in vitro and within infected macrophages. T6SS dynamics and function depends on the general purpose ClpB unfoldase, which specifically colocalizes with contracted sheaths and is required for their disassembly...
June 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28618410/deletion-of-the-inflammasome-sensor-aim2-mitigates-a%C3%AE-deposition-and-microglial-activation-but-increases-inflammatory-cytokine-expression-in-an-alzheimer-disease-mouse-model
#6
Pei-Jung Wu, Yun-Fen Hung, Hsin-Yu Liu, Yi-Ping Hsueh
OBJECTIVE: Inflammation is clearly associated with Alzheimer disease (AD). Knockout of Nlrp3, a gene encoding an inflammasome sensor, has been shown to ameliorate AD pathology in a mouse model. Because AIM2 is the most dominant inflammasome sensor expressed in mouse brains, here we investigate whether Aim2 deletion also influences the phenotype of a 5XFAD AD mouse model. METHODS: Quantitative RT-PCR, immunostaining, immunoblotting, and behavioral analyses were applied to compare wild-type, Aim2-/-, 5XFAD, and Aim2-/-;5XFAD mice...
June 16, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28580773/hbx-mediated-decrease-of-aim2-contributes-to-hepatocellular-carcinoma-metastasis
#7
Shi-Lu Chen, Li-Li Liu, Shi-Xun Lu, Rong-Zhen Luo, Chun-Hua Wang, Hong Wang, Shao-Hang Cai, Xia Yang, Dan Xie, Chris Zhiyi Zhang, Jing-Ping Yun
Tumor metastasis is responsible for the high mortality rates in patients with hepatocellular carcinoma (HCC). Absent in Melanoma 2 (AIM2) has been implicated in inflammation and carcinogenesis, but its role in HCC metastasis remains unknown. Here, we show that AIM2 protein expression was noticeably reduced in HCC cell lines and clinical samples. A reduction in AIM2 was closely associated with higher serum AFP levels, vascular invasion, poor tumor differentiation, an incomplete tumor capsule and unfavorable postsurgical survival odds...
June 5, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28526809/tumor-cell-specific-aim2-regulates-growth-and-invasion-of-cutaneous-squamous-cell-carcinoma
#8
Mehdi Farshchian, Liisa Nissinen, Elina Siljamäki, Pilvi Riihilä, Minna Piipponen, Atte Kivisaari, Markku Kallajoki, Reidar Grénman, Juha Peltonen, Sirkku Peltonen, Koen D Quint, Jan Nico Bouwes Bavinck, Veli-Matti Kähäri
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. Inflammation is a typical feature in cSCC progression. Analysis of the expression of inflammasome components in cSCC cell lines and normal human epidermal keratinocytes revealed upregulation of the expression of AIM2 mRNA and protein in cSCC cells. Elevated levels of AIM2 mRNA were noted in cSCCs in vivo compared with normal skin. Strong and moderate tumor cell specific expression of AIM2 was detected with immunohistochemistry (IHC) in sporadic human cSCCs in vivo, whereas expression of AIM2 was moderate in cSCC in situ (cSCCIS) and low or absent in actinic keratosis (AK) and normal skin...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524163/an-evolving-function-of-dna-containing-exosomes-in-chemotherapy-induced-immune-response
#9
Paul Kurywchak, Raghu Kalluri
Chemotherapy is a predominant strategy to treat cancer and is often associated with toxicities like severe diarrhea that puts patients at additional risk and can hinder treatment strategies. Lian et al. recently explored the immune-mediated mechanisms of Irinotecan-induced diarrhea in colorectal cancer and found that double-stranded DNA in small vesicles can launch inflammation pathways in immune cells through the cytosolic DNA sensor AIM2.
June 2017: Cell Research
https://www.readbyqxmd.com/read/28516116/asc-particle-induced-peritonitis
#10
Lucia de Almeida, Andrea Dorfleutner, Christian Stehlik
In response to pathogen infection and tissue damage, inflammasome sensors such as NLRP3 and AIM2 are activated, which triggers PYRIN domain (PYD)-mediated ASC nucleation, followed by self-perpetuating ASC polymerization, which ultimately culminates in caspase-1 activation, interleukin (IL)-1β and IL-18 processing and release and pyroptosis (Ratsimandresy et al., 2013; Cai et al., 2014). Inflammasomes release not only cytokines, but also the polymeric ASC danger particles (pASC) by pyroptosis, which perpetuate and propagate inflammasome responses to bystander cells to engage cell intrinsic ASC and caspase-1 (Baroja-Mazo et al...
October 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28480966/human-cytomegalovirus-triggers-the-assembly-of-aim2-inflammasome-in-thp-1-derived-macrophages
#11
Yuan Huang, Lingling Liu, Di Ma, Yi Liao, Yuanyuan Lu, Heyu Huang, Wenqing Qin, Xinglou Liu, Feng Fang
Absent in melanoma 2 (AIM2) inflammasome is a multiprotein complex which plays a pivotal role in the host immune response to multiple pathogens. The role of AIM2 in human cytomegalovirus (HCMV) infection is poorly studied. Thus, using a small inference RNA (siRNA) approach and THP-1 derived macrophage cells infected with HCMV AD169 strain, we investigated the impact of HCMV infection on AIM2-mediated molecular events. Compared to wild-type cells, AIM2-defiecient macrophages showed a limited ability to activate caspase-1, process IL-1β, and induce cell death...
May 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28465544/lentinan-from-shiitake-selectively-attenuates-aim2-and-non-canonical-inflammasome-activation-while-inducing-pro-inflammatory-cytokine-production
#12
Huijeong Ahn, Eunsaem Jeon, Jin-Chul Kim, Seung Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Pyeung-Hyeun Kim, Geun-Shik Lee
Lentinan extracted from shiitake (Lentinula edodes) is a β-glucan that has been reported as an intravenous anti-tumor polysaccharide via enhancement of the host immune system. In this study, we determined the effect of lentinan on inflammasome activation, a multi-protein platform, in myeloid cells. Mouse bone marrow-derived macrophages were treated with lentinan with/without inflammasome triggers, and maturation of interleukin (IL)-1β, IL-18, or caspase-1 was measured as a readout of inflammasome activation...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28463821/mitochondrial-ros-induced-by-chronic-ethanol-exposure-promote-hyper-activation-of-the-nlrp3-inflammasome
#13
Laura R Hoyt, Matthew J Randall, Jennifer L Ather, Daniel P DePuccio, Christopher C Landry, Xi Qian, Yvonne M Janssen-Heininger, Albert van der Vliet, Anne E Dixon, Eyal Amiel, Matthew E Poynter
Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28424239/aim2-inflammasome-is-critical-for-influenza-induced-lung-injury-and-mortality
#14
Hongbo Zhang, Jiadi Luo, John F Alcorn, Kong Chen, Songqing Fan, Joseph Pilewski, Aizhong Liu, Wei Chen, Jay K Kolls, Jieru Wang
The absent in melanoma 2 (AIM2) inflammasome plays an important role in many viral and bacterial infections, but very little is known about its role in RNA virus infection, including influenza A virus (IAV). In this study, we have designed in vivo and in vitro studies to determine the role of AIM2 in infections with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase-1 activation and release of cleaved IL-1β in the lung, which was significantly reduced in AIM2-deficient mice...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28409562/chemotherapy-induced-intestinal-inflammatory-responses-are-mediated-by-exosome-secretion-of-double-strand-dna-via-aim2-inflammasome-activation
#15
Qiaoshi Lian, Jun Xu, Shanshan Yan, Min Huang, Honghua Ding, Xiaoyu Sun, Aiwei Bi, Jian Ding, Bing Sun, Meiyu Geng
Chemotherapies are known often to induce severe gastrointestinal tract toxicity but the underlying mechanism remains unclear. This study considers the widely applied cytotoxic agent irinotecan (CPT-11) as a representative agent and demonstrates that treatment induces massive release of double-strand DNA from the intestine that accounts for the dose-limiting intestinal toxicity of the compound. Specifically, "self-DNA" released through exosome secretion enters the cytosol of innate immune cells and activates the AIM2 (absent in melanoma 2) inflammasome...
June 2017: Cell Research
https://www.readbyqxmd.com/read/28397969/aim2-inflammasome-is-associated-with-disease-severity-in-tegumentary-leishmaniasis-caused-by-leishmania-v-braziliensis
#16
R B Moreira, C Pirmez, M P de Oliveira-Neto, L S Aguiar, A J S Gonçalves, L O R Pereira, L Abreu, M P De Oliveira
The inflammasome is a multiprotein signalling platform involved in the pathogenesis of various inflammatory skin diseases. Herein, we investigated gene and protein expression of the inflammasome molecules AIM2 and NLRP3 in active lesions from patients with L. (V.) braziliensis-associated tegumentary leishmaniasis (TL) and correlated these findings with the clinical presentations and responses to therapy. Real-time PCR assays showed a significantly higher AIM2 gene expression in mucosal leishmaniasis (ML) compared with that in cutaneous leishmaniasis (CL)...
April 11, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28397782/papilloma-pseudovirus-eradicates-intestinal-tumours-and-triples-the-lifespan-of-apc-min-mice
#17
Zhenyu Zhong, Yougang Zhai, Ping Bu, Shivanee Shah, Liang Qiao
Inducing tumour-specific adaptive immunity, such as cytotoxic T lymphocyte (CTL) response, can result in promising antitumour effect against several human malignancies, especially in combination with immune checkpoint blockade strategies. However, little is known whether activation of innate immunity can lead to direct tumoricidal effect. Here, we develop a papilloma pseudovirus-based oral immunotherapeutic approach that shows strong tumoricidal effects in the gut, resulting in an almost tripled lifespan of Apc(Min/+) mice (an animal model of human intestinal tumorigenesis)...
April 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28387608/common-polymorphisms-in-ifi16-and-aim2-genes-are-associated-with-periodontal-disease
#18
Julie T Marchesan, Yizu Jiao, Kevin Moss, Kimon Divaris, William Seaman, Jennifer Webster-Cyriaque, Shaoping Zhang, Ning Yu, Catharine Song, Sompop Bencharit, Ricardo Teles, Steven Offenbacher
BACKGROUND: The single nucleotide polymorphism (SNP) context of a previously identified periodontitis-associated locus is investigated, and its association with microbial, biologic, and periodontal disease clinical parameters is examined. METHODS: A 200-kb spanning region of 1q12 previously highlighted in a genome-wide association scan among 4,766 European American individuals (SNP rs1633266) was annotated. Two haplotype blocks were selected. Association of these polymorphisms with data on microbial plaque composition, gingival crevicular fluid (GCF)-interleukin (IL)-1β levels, and clinical parameters of periodontal disease were examined...
July 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28369146/epstein-barr-virus-infection-induced-inflammasome-activation-in-human-monocytes
#19
Yuka Torii, Jun-Ichi Kawada, Takayuki Murata, Hironori Yoshiyama, Hiroshi Kimura, Yoshinori Ito
Inflammasomes are cytoplasmic sensors that regulate the activity of caspase-1 and the secretion of interleukin-1β (IL-1β) or interleukin-18 (IL-18) in response to foreign molecules, including viral pathogens. They are considered to be an important link between the innate and adaptive immune responses. However, the mechanism by which inflammasome activation occurs during primary Epstein-Barr virus (EBV) infection remains unknown. Human B lymphocytes and epithelial cells are major targets of EBV, although it can also infect a variety of other cell types...
2017: PloS One
https://www.readbyqxmd.com/read/28347828/protective-effects-of-cinnamomum-cassia-lamaceae-against-gout-and-septic-responses-via-attenuation-of-inflammasome-activation-in-experimental-models
#20
Woo-Young Shin, Do-Wan Shim, Myong-Ki Kim, Xiao Sun, Sushruta Koppula, Sang-Hyeun Yu, Han-Bi Kim, Tack-Joong Kim, Tae-Bong Kang, Kwang-Ho Lee
ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia (C. cassia, Lauraceae family), commonly used for treating dyspepsia, gastritis, blood circulation, and inflammatory diseases is considered as one of the 50 fundamental herbs in traditional Chinese medicine. AIM OF THE STUDY: The anti-inflammatory action of an ethanol extract of C. cassia (CA), and its underlying mechanisms were explored in both in vitro cellular and in vivo murine models. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of CA on inflammasome activation...
March 24, 2017: Journal of Ethnopharmacology
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