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https://www.readbyqxmd.com/read/29045388/inflammatory-memory-sensitizes-skin-epithelial-stem-cells-to-tissue-damage
#1
Shruti Naik, Samantha B Larsen, Nicholas C Gomez, Kirill Alaverdyan, Ataman Sendoel, Shaopeng Yuan, Lisa Polak, Anita Kulukian, Sophia Chai, Elaine Fuchs
The skin barrier is the body's first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells...
October 18, 2017: Nature
https://www.readbyqxmd.com/read/29033131/oxysterol-restraint-of-cholesterol-synthesis-prevents-aim2-inflammasome-activation
#2
Eric V Dang, Jeffrey G McDonald, David W Russell, Jason G Cyster
Type I interferon restrains interleukin-1β (IL-1β)-driven inflammation in macrophages by upregulating cholesterol-25-hydroxylase (Ch25h) and repressing SREBP transcription factors. However, the molecular links between lipid metabolism and IL-1β production remain obscure. Here, we demonstrate that production of 25-hydroxycholesterol (25-HC) by macrophages is required to prevent inflammasome activation by the DNA sensor protein absent in melanoma 2 (AIM2). We find that in response to bacterial infection or lipopolysaccharide (LPS) stimulation, macrophages upregulate Ch25h to maintain repression of SREBP2 activation and cholesterol synthesis...
October 7, 2017: Cell
https://www.readbyqxmd.com/read/29033128/the-dna-inflammasome-in-human-myeloid-cells-is-initiated-by-a-sting-cell-death-program-upstream-of-nlrp3
#3
Moritz M Gaidt, Thomas S Ebert, Dhruv Chauhan, Katharina Ramshorn, Francesca Pinci, Sarah Zuber, Fionan O'Duill, Jonathan L Schmid-Burgk, Florian Hoss, Raymund Buhmann, Georg Wittmann, Eicke Latz, Marion Subklewe, Veit Hornung
Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3...
October 7, 2017: Cell
https://www.readbyqxmd.com/read/29030458/a-noncanonical-function-of-cgamp-in-inflammasome-priming-and-activation
#4
Karen V Swanson, Robert D Junkins, Cathryn J Kurkjian, Elizabeth Holley-Guthrie, Avani A Pendse, Rachid El Morabiti, Alex Petrucelli, Glen N Barber, Chris A Benedict, Jenny P-Y Ting
Recognition of pathogen-associated molecular patterns and danger-associated molecular patterns by host cells is an important step in innate immune activation. The DNA sensor cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to stimulator of interferon genes (STING) to activate IFN-I. Here we show that cGAMP has a noncanonical function in inflammasome activation in human and mouse cells. Inflammasome activation requires two signals, both of which are activated by cGAMP...
October 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28976036/overexpression-of-nlrp3-nlrc4-and-aim2-inflammasomes-and-their-priming-associated-molecules-tlr2-tlr4-dectin-1-dectin-2-and-nf%C3%AE%C2%BAb-in-malassezia-folliculitis
#5
Ni Liang, Yan-Ping Yang, Wei Li, Ya-Yun Wu, Zi-Wei Zhang, Yun Luo, Yi-Ming Fan
BACKGROUND: The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear. OBJECTIVES: To determine expression of four canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion. METHODS: Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects...
October 4, 2017: Mycoses
https://www.readbyqxmd.com/read/28968459/ifn-%C3%AE-extends-the-immune-functions-of-guanylate-binding-proteins-to-inflammasome-independent-antibacterial-activities-during-francisella-novicida-infection
#6
Pierre Wallet, Sacha Benaoudia, Amandine Mosnier, Brice Lagrange, Amandine Martin, Helena Lindgren, Igor Golovliov, Fanny Michal, Pauline Basso, Sophia Djebali, Angelina Provost, Omran Allatif, Etienne Meunier, Petr Broz, Masahiro Yamamoto, Bénédicte F Py, Eric Faudry, Anders Sjöstedt, Thomas Henry
Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i) GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii) GBPs would directly facilitate inflammasome complex assembly...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28963531/methylene-blue-inhibits-nlrp3-nlrc4-aim2-and-non-canonical-inflammasome-activation
#7
Huijeong Ahn, Seung Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Pyeung-Hyeun Kim, Eui-Ju Hong, Beum-Soo An, Eunsong Lee, Geun-Shik Lee
Methylene blue (MB), which has antioxidant, anti-inflammatory, neuroprotective, and mitochondria protective effects, has been widely used as a dye and medication. However, the effect of MB on inflammasome activation has not yet been studied. Inflammasomes are multi-protein complexes that induce maturation of interleukins (ILs)-1β and -18 as well as caspase-1-mediated cell death, known as pyroptosis. Dysregulation of inflammasomes causes several diseases such as type 2 diabetes, Alzheimer's disease, and gout...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28947539/priming-and-activation-of-inflammasome-by-canarypox-virus-vector-alvac-via-the-cgas-ifi16-sting-type-i-ifn-pathway-and-aim2-sensor
#8
Fengliang Liu, Qingli Niu, Xiuzhen Fan, Connie Liu, Jie Zhang, Zhi Wei, Wei Hou, Thirumala-Devi Kanneganti, Merlin L Robb, Jerome H Kim, Nelson L Michael, Jiaren Sun, Lynn Soong, Haitao Hu
Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of human diseases including HIV/AIDS. Less is known about the mechanisms underlying the host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. In this study, we investigated the innate interactions of APCs with two commonly used HIV vaccine vectors, ALVAC and Ad5, and identified AIM2 as an innate sensor for ALVAC, triggering strong inflammasome activation in both human and mouse APCs...
September 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28935571/aggravated-post-infarct-heart-failure-in-type-2-diabetes-is-associated-with-impaired-mitophagy-and-exaggerated-inflammasome-activation
#9
Thota Durga Devi, Mohan Babu, Petri Mäkinen, Minna Kaikkonen, Merja Heinaniemi, Hanne Laakso, Elias Ylä-Herttuala, Lassi Rieppo, Timo Liimatainen, Nikolay Naumenko, Pasi Tavi, Seppo Ylä-Herttuala
Type 2 diabetes mellitus (T2DM) is a major risk factor for heart disease. Mortality rates following myocardial infarction (MI) are significantly increased in T2DM patients due to dysfunctional left ventricle (LV). However, molecular pathways underlying accelerated post-MI heart failure (HF) in T2DM remain unclear. We investigated the underlying mechanisms by inducing MI in a well-established model of T2DM and control mice. Cardiac imaging revealed a significantly decreased global LV ejection fraction (EF) in parallel with increased mortality post-MI in T2DM mice compared to controls...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28928425/double-deficiency-of-trex2-and-dnase1l2-nucleases-leads-to-accumulation-of-dna-in-lingual-cornifying-keratinocytes-without-activating-inflammatory-responses
#10
Joan Manils, Heinz Fischer, Joan Climent, Eduard Casas, Celia García-Martínez, Jordi Bas, Supawadee Sukseree, Tanya Vavouri, Francisco Ciruela, Josep Maria de Anta, Erwin Tschachler, Leopold Eckhart, Concepció Soler
The cornification of keratinocytes on the surface of skin and oral epithelia is associated with the degradation of nuclear DNA. The endonuclease DNase1L2 and the exonuclease Trex2 are expressed specifically in cornifying keratinocytes. Deletion of DNase1L2 causes retention of nuclear DNA in the tongue epithelium but not in the skin. Here we report that lack of Trex2 results in the accumulation of DNA fragments in the cytoplasm of cornifying lingual keratinocytes and co-deletion of DNase1L2 and Trex2 causes massive accumulation of DNA fragments throughout the cornified layers of the tongue epithelium...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890719/outer-membrane-vesicles-prime-and-activate-macrophage-inflammasomes-and-cytokine-secretion-in-vitro-and-in-vivo
#11
Jessica D Cecil, Neil M O'Brien-Simpson, Jason C Lenzo, James A Holden, William Singleton, Alexis Perez-Gonzalez, Ashley Mansell, Eric C Reynolds
Outer membrane vesicles (OMVs) are proteoliposomes blebbed from the surface of Gram-negative bacteria. Chronic periodontitis is associated with an increase in subgingival plaque of Gram-negative bacteria, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. In this study, we investigated the immune-modulatory effects of P. gingivalis, T. denticola, and T. forsythia OMVs on monocytes and differentiated macrophages. All of the bacterial OMVs were phagocytosed by monocytes, M(naïve) and M(IFNγ) macrophages in a dose-dependent manner...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28886908/dna-sensing-across-the-tree-of-life
#12
REVIEW
Stefania Gallucci, Massimo E Maffei
From plants to mammals, pattern recognition receptors (PRRs) specifically recognize DNA, as a potential marker of either infection or damage. These receptors play critical roles in inflammation, immunity, and pathogen resistance. Importantly, given the ubiquity of DNA, its sensing must be tightly regulated. DNA localization plays a key role in recognition, as highlighted by Toll-like receptor 9 (TLR9) in the endosomal compartment and cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) in the cytoplasm...
October 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28875942/inflammasome-dependent-mechanisms-involved-in-sensing-and-restriction-of-bacterial-replication
#13
Warrison A Andrade, Dario S Zamboni
Inflammasomes are multiprotein platforms assembled in the cytosol in response to pathogens and cell stress. Inflammasomes are recognized by their important role on defenses against bacterial infections and have been also implicated in a range of human inflammatory disorders. Intracellular sensors such as NLRP1, NLRP3, NLRC4, AIM2 and Pyrin induce assembly of inflammasomes, while caspase-11 induces the non-canonical pathway for activation of the NLRP3 inflammasome. The formation of the inflammasome leads to caspase-1 activation that triggers pyroptosis and activation of interleukin-1β (IL-1β) and IL-18...
September 6, 2017: Current Issues in Molecular Biology
https://www.readbyqxmd.com/read/28867284/crp-polymorphisms-and-dna-methylation-of-the-aim2-gene-influence-associations-between-trauma-exposure-ptsd-and-c-reactive-protein
#14
M W Miller, H Maniates, E J Wolf, M W Logue, S A Schichman, A Stone, W Milberg, R McGlinchey
BACKGROUND: Recent studies have implicated inflammatory processes in the pathophysiology of posttraumatic stress disorder (PTSD). C-reactive protein (CRP) is a widely-used measure of peripheral inflammation, but little is known about the genetic and epigenetic factors that influence blood levels of C-reactive protein (CRP) in individuals with PTSD. METHODS: Participants were 286 U.S. military veterans of post-9/11 conflicts (57% with current PTSD). Analyses focused on single nucleotide polymorphisms (SNPs) in the CRP gene and DNA methylation at cg10636246 in AIM2-a locus recently linked to CRP levels through results from a large-scale epigenome-wide association study...
August 31, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28855232/molecular-mechanisms-of-inflammasome-signaling
#15
REVIEW
Anukriti Mathur, Jenni A Hayward, Si Ming Man
The inflammasome is a macromolecular protein complex that mediates proteolytic cleavage of pro-IL-1β and -IL-18 and induces cell death in the form of pyroptosis. Certain nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), or tripartite motif (TRIM) family receptors trigger the assembly of an inflammasome in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Recent studies have revealed a multitude of host components and signals that are essential for controlling canonical and noncanonical inflammasome activation and pyroptosis...
August 30, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28846926/cirtical-role-for-salmonella-effector-sopb-in-regulating-inflammasome-activation
#16
Gui-Qiu Hu, Pei-Xuan Song, Wei Chen, Shuai Qi, Shui-Xing Yu, Chong-Tao Du, Xu-Ming Deng, Hong-Sheng Ouyang, Yong-Jun Yang
OBJECTIVE: Salmonella is known to evolve many mechanisms to avoid or delay inflammasome activation which remain largely unknown. In this study, we investigated whether the SopB protein critical to bacteria virulence capacity was an effector that involved in the regulation of inflammasome activation. METHODS: BMDMs from NLRC4-, NLRP3-, caspase-1/-11-, IFI16- and AIM2-deficient mice were pretreated with LPS, and subsequently stimulated with a series of SopB-related strains of Salmonella, inflammasome induced cell death, IL-1β secretion, cleaved caspase-1 production and ASC speckle formation were detected...
October 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28813641/aim2-inflammasome-activation-and-regulation-a-structural-perspective
#17
Bing Wang, Qian Yin
Absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple steps is the assembly of high-order structures, especially helical filaments nucleated by upstream molecules, rather than stoichiometric complexes...
August 13, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28809949/maturation-dependent-expression-of-aim2-in-human-b-cells
#18
Alexandra Svensson, Marianela Patzi Churqui, Kerstin Schlüter, Liza Lind, Kristina Eriksson
Intracellular DNA- and RNA-sensing receptors, such as the IFN-inducible protein Absent in Melanoma 2 (AIM2), serve as host sensors against a wide range of infections. Immune sensing and inflammasome activation by AIM2 has been implicated in innate antiviral recognition in many experimental systems using cell-lines and animal models. However, little is known about the expression and function of AIM2 in freshly isolated human cells. In this study we investigated the expression of AIM2 in different cell types derived from human cord and adult peripheral blood, in steady state and following in vitro-activation...
2017: PloS One
https://www.readbyqxmd.com/read/28802238/expression-and-clinical-significance-of-absent-in-melanoma-2-in-colorectal-cancer
#19
Zhi Zhang, Xiaoqiang Dong, Xiaodong Yang, Daiwei Wan, Liang Sun, Mengmeng Gu, Ming Li, Zheng Zhu, Jin Wang, Zengfu Shang, Songbing He
Increasing research has indicated that absent in melanoma 2 (AIM2) is aberrantly expressed in several tumor types. However, the association between AIM2 expression and clinicopathological factors or prognosis of patient with colorectal cancer (CRC) remains elusive. In the present study, we first examined the protein and mRNA expression of AIM2 in CRC cell lines by western blotting and quantitative RT-PCR (qRT-PCR). Then, we detected AIM2 expression in CRC tissue using western blotting and immunohistochemistry (IHC) respectively to evaluate its clinicopathological characteristics and prognosis in CRC...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28790368/signs-of-innate-immune-activation-and-premature-immunosenescence-in-psoriasis-patients
#20
Liisi Šahmatova, Elena Sügis, Marina Šunina, Helen Hermann, Ele Prans, Maire Pihlap, Kristi Abram, Ana Rebane, Hedi Peterson, Pärt Peterson, Külli Kingo, Kai Kisand
Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors...
August 8, 2017: Scientific Reports
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