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https://www.readbyqxmd.com/read/28533780/innate-immune-function-of-mitochondrial-metabolism
#1
REVIEW
David Sancho, Michel Enamorado, Johan Garaude
Sensing of microbe-associated molecular patterns or danger signals by innate immune receptors drives a complex exchange of information. Innate receptor signaling not only triggers transcriptional events but also induces profound changes in metabolic fluxes, redox balance, and metabolite abundance thereby influencing immune cell function. Mitochondria are at the core of metabolic adaptation to the changing environment. The close interaction between mitochondrial metabolism and immune signaling has emerged as a central regulator of innate sensing...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#2
Sannula Kesavardhana, Thirumala-Devi Kanneganti
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein - apoptosis associated speck-like protein containing a caspase-activation and -recruitment domain (ASC) - activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens...
May 20, 2017: International Immunology
https://www.readbyqxmd.com/read/28531130/comparative-safety-and-efficacy-profile-of-a-novel-oil-in-water-vaccine-adjuvant-comprising-vitamins-a-and-e-and-a-catechin-in-protective-anti-influenza-immunity
#3
Sapna Patel, Yasser Faraj, Debra K Duso, William W Reiley, Erik A Karlsson, Stacey Schultz-Cherry, Michael Vajdy
Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA) mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS), based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus...
May 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28530643/danger-signals-in-regulating-the-immune-response-to-solid-organ-transplantation
#4
Jamie L Todd, Scott M Palmer
Endogenous danger signals, or damage-associated molecular patterns (DAMPs), are generated in response to cell stress and activate innate immunity to provide a pivotal mechanism by which an organism can respond to damaged self. Accumulating experimental and clinical data have established the importance of DAMPs, which signal through innate pattern recognition receptors (PRRs) or DAMP-specific receptors, in regulating the alloresponse to solid organ transplantation (SOT). Moreover, DAMPs may incite distinct downstream cellular responses that could specifically contribute to the development of allograft fibrosis and chronic graft dysfunction...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28524859/mesenchymal-stem-cells-sense-mitochondria-released-from-damaged-cells-as-danger-signals-to-activate-their-rescue-properties
#5
Meriem Mahrouf-Yorgov, Lionel Augeul, Claire Crola Da Silva, Maud Jourdan, Muriel Rigolet, Sylvie Manin, René Ferrera, Michel Ovize, Adeline Henry, Aurélie Guguin, Jean-Paul Meningaud, Jean-Luc Dubois-Randé, Roberto Motterlini, Roberta Foresti, Anne-Marie Rodriguez
Mesenchymal stem cells (MSCs) protect tissues against cell death induced by ischemia/reperfusion insults. This therapeutic effect seems to be controlled by physiological cues released by the local microenvironment following injury. Recent lines of evidence indicate that MSC can communicate with their microenvironment through bidirectional exchanges of mitochondria. In particular, in vitro and in vivo studies report that MSCs rescue injured cells through delivery of their own mitochondria. However, the role of mitochondria conveyed from somatic cells to MSC remains unknown...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28521686/prothymosin-alpha-an-alarmin-and-more
#6
Pinelopi Samara, Chrysoula-Evangelia Karachaliou, Kyriaki Ioannou, Nikos E Papaioannou, Ioannis F Voutsas, Christos Zikos, Ioannis Pirmettis, Minas Papadopoulos, Hubert Kalbacher, Evangelia Livaniou, Ourania E Tsitsilonis, Wolfgang Voelter
BACKGROUND/OBJECTIVE: Prothymosin alpha (proTα) is a ubiquitous polypeptide first isolated by Haritos in 1984, whose role still remains partly elusive. We know that proTα acts both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similarly to molecules termed "alarmins". Our research team pioneered the elucidation of the mechanisms underlying the observed activities of proTα. RESULTS: We were the first to demonstrate that proTα levels increase during normal and abnormal cell proliferation...
May 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28516117/reconstruction-of-the-mouse-inflammasome-system-in-hek293t-cells
#7
Hexin Shi, Anne Murray, Bruce Beutler
The NLRP3 (NLR family, Pyrin domain containing 3) inflammasome is a multiprotein complex comprised of NLRP3, pro-caspase-1, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and the protein kinase NIMA related kinase 7 (NEK7) (Shi et al., 2016; He et al., 2016; Schmid-Burgk et al., 2016). When cells are exposed to microbes and/or danger signals, the inflammasome assembles and serves as a platform for the activation of caspase-1. Caspase-1 activation promotes the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-18, and IL-33 as well as pyroptosis induction (Gross et al...
November 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28516116/asc-particle-induced-peritonitis
#8
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/28515391/advanced-glycation-end-products-regulate-interleukin-1%C3%AE-production-in-human-placenta
#9
Kotomi Seno, Saoko Sase, Ayae Ozeki, Hironori Takahashi, Akihide Ohkuchi, Hirotada Suzuki, Shigeki Matsubara, Hisataka Iwata, Takehito Kuwayama, Koumei Shirasuna
Maternal obesity is a major risk factor for pregnancy complications, causing inflammatory cytokine release in the placenta, including interleukin-1β (IL-1β), IL-6, and IL-8. Pregnant women with obesity develop accelerated systemic and placental inflammation with elevated circulating advanced glycation end products (AGEs). IL-1β is a pivotal inflammatory cytokine associated with obesity and pregnancy complications, and its production is regulated by NLR family pyrin domain-containing 3 (NLRP3) inflammasomes...
May 18, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28513821/platelets-in-sepsis-are-there-any-new-aspects
#10
Małgorzata Lipinska-Gediga
Platelets display a number of properties besides the crucial function of repairing a damaged vascular endothelium and stopping bleeding. Platelets constitutively express molecules that are classically acknowledged to function in primary haemostasis. Platelets specialize in pro-inflammatory activities, and can secrete a large number of molecules, many of which display biological response modifier functions. Recently, platelets expressing receptors for infectious and possibly non-infectious danger signals were shown to be involved in pathophysiological reactions including an immune-inflammatory response...
May 17, 2017: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/28507789/calreticulin-promotes-immunity-and-type-i-interferon-dependent-survival-in-mice-with-acute-myeloid-leukemia
#11
Xiufen Chen, Dominick Fosco, Douglas E Kline, Justin Kline
Exposure of cancer cells to particular chemotherapeutic agents or γ-irradiation induces a form of cell death that stimulates an immune response in mice. This "immunogenic cell death" requires calreticulin (CRT) translocation to the plasma membrane, which has been shown to promote cancer cell phagocytosis. However, it remains unclear whether the effect of CRT on cancer cell phagocytosis is alone sufficient to affect tumor immunity. Acute myeloid leukemia (AML) cells expressing cell-surface CRT were generated in order to characterize the mechanism(s) through which CRT activates tumor immune responses...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28505322/exosomes-in-toxicology-relevance-to-chemical-exposure-and-pathogenesis-of-environmentally-linked-diseases
#12
Dilshan S Harischandra, Shivani Ghaisas, Dharmin Rokad, Anumantha G Kanthasamy
Chronic exposure to environmental toxins has been known to initiate or aggravate various neurological disorders, carcinomas and other adverse health effects. Uptake by naïve cells of pathogenic factors such as danger-associated molecules, mRNAs, miRNAs or aggregated proteins leads to disruption in cellular homeostasis further resulting in inflammation and disease propagation. While early research tended to focus solely on exosomal removal of unwanted cellular contents, more recent reports indicate that these nano-vesicles play an active role in intercellular signaling...
May 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28497028/inactive-gingipains-from-p-gingivalis-selectively-skews-t-cells-toward-a-th17-phenotype-in-an-il-6-dependent-manner
#13
Izabela Glowczyk, Alicia Wong, Barbara Potempa, Olena Babyak, Maciej Lech, Richard J Lamont, Jan Potempa, Joanna Koziel
Gingipain cysteine proteases are considered key virulence factors of Porphyromonas gingivalis. They significantly influence antibacterial and homeostatic functions of macrophages, neutrophils, the complement system, and cytokine networks. Recent data indicate the role of P. gingivalis in T cell differentiation; however, the involvement of gingipains in this process remains elusive. Therefore, the aim of this study was to investigate the contribution of danger signals triggered by the gingipains on the generation of Th17 cells, which play a key role in protection against bacterial diseases but may cause chronic inflammation and bone resorption...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28495959/potential-nematode-alarm-pheromone-induces-acute-avoidance-in-caenorhabditis-elegans
#14
Ying Zhou, Mario Loeza-Cabrera, Zheng Liu, Boanerges Aleman-Meza, Julie K Nguyen, Sang-Kyu Jung, Yuna Choi, Qingyao Shou, Rebecca A Butcher, Weiwei Zhong
It is crucial for animal survival to detect dangers such as predators. A good indicator of dangers is injury of conspecifics. Here we show that fluids released from injured conspecifics invoke acute avoidance in both free-living and parasitic nematodes. Caenorhabditis elegans avoids extracts from closely related nematode species but not fruit fly larvae. The worm extracts have no impact on animal lifespan, suggesting that the worm extract may function as an alarm instead of inflict physical harm. Avoidance of the worm extract requires the function of a cGMP signaling pathway that includes the cGMP-gated channel TAX-2/TAX-4 in the amphid sensory neurons ASI and ASK...
May 11, 2017: Genetics
https://www.readbyqxmd.com/read/28486191/nlrp4-is-an-essential-negative-regulator-of-fructose-induced-cardiac-injury-in-vitro-and-in-vivo
#15
Yong-Gang Lian, Hai-Ying Zhao, Sheng-Ji Wang, Qin-Liang Xu, Xiang-Jun Xia
High fructose consumption leads to metabolic syndrome and enhances cardiovascular disease risk. However, our knowledge of the molecular mechanism underlying the cardiac disease caused by fructose feeding is still poor. Nod-like receptors (NLRs) are intracellular sensors, responding to a variety of intracellular danger signals to induce injuries. NLRP4 is a negative regulator of nuclear factor-κB (NF-κB) signaling pathway through interactions with kinase IκB kinase (IKK). Here, we illustrated that NLRP4 attenuates pro-inflammatory cytokines releasing, including Transforming growth factor (TGF-β1), Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6), in fructose-treated cardiac cells by means of RT-qPCR, and western blotting analysis...
May 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28479485/new-insights-into-the-pathogenesis-of-giant-cell-arteritis
#16
REVIEW
Francesco Ciccia, Aroldo Rizzo, Angelo Ferrante, Giuliana Guggino, Stefania Croci, Alberto Cavazza, Carlo Salvarani, Giovanni Triolo
Giant cell arteritis (GCA) is an inflammatory chronic disease occurring exclusively in elderly individuals. Until recently, the disease has been considered a unique disease resulting from the interaction in the walls of susceptible arteries, between an unknown infectious agents with local dendritic cells (DCs), activated CD4 T cells and effector macrophages. Recent evidence has shown that this view was too simplistic and has clarified many of the pathogenetic aspects of the disease. Many genetic studies recently published have identified different new genes, including cytokines, adhesion molecules and regulators of innate immunity, as crucial players in the development and progression of GCA...
May 4, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28476750/programming-and-memory-dynamics-of-innate-leukocytes-during-tissue-homeostasis-and-inflammation
#17
REVIEW
Christina Lee, Shuo Geng, Yao Zhang, Allison Rahtes, Liwu Li
The field of innate immunity is witnessing a paradigm shift regarding "memory" and "programming" dynamics. Past studies of innate leukocytes characterized them as first responders to danger signals with no memory. However, recent findings suggest that innate leukocytes, such as monocytes and neutrophils, are capable of "memorizing" not only the chemical nature but also the history and dosages of external stimulants. As a consequence, innate leukocytes can be dynamically programmed or reprogrammed into complex inflammatory memory states...
May 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28476120/central-peptidergic-modulation-of-peripheral-olfactory-responses
#18
Sion Lee, Young-Joon Kim, Walton D Jones
BACKGROUND: Animal olfactory systems detect volatile environmental chemicals and integrate this information to direct the discovery of food and mates as well as danger avoidance. Rather than remaining constant, olfactory response thresholds are modulated by internal and external cues to adapt odor-guided behaviors to changing conditions. RESULTS: Here, we show in Drosophila melanogaster that neuropeptide F (NPF) modulates the responses of a specific population of antennal olfactory sensory neurons (OSNs) to food-derived odors...
May 5, 2017: BMC Biology
https://www.readbyqxmd.com/read/28467380/nanosecond-pulsed-dbd-plasma-generated-reactive-oxygen-species-trigger-immunogenic-cell-death-in-a549-lung-carcinoma-cells-through-intracellular-oxidative-stress
#19
Abraham Lin, Billy Truong, Sohil Patel, Nagendra Kaushik, Eun Ha Choi, Gregory Fridman, Alexander Fridman, Vandana Miller
A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death...
May 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28465465/nlrp3-inflammasome-assembly-is-regulated-by-phosphorylation-of-the-pyrin-domain
#20
Andrea Stutz, Carl-Christian Kolbe, Rainer Stahl, Gabor L Horvath, Bernardo S Franklin, Olivia van Ray, Rebecca Brinkschulte, Matthias Geyer, Felix Meissner, Eicke Latz
NLRP3 is a cytosolic pattern recognition receptor that senses microbes and endogenous danger signals. Upon activation, NLRP3 forms an inflammasome with the adapter ASC, resulting in caspase-1 activation, release of proinflammatory cytokines and cell death. How NLRP3 activation is regulated by transcriptional and posttranslational mechanisms to prevent aberrant activation remains incompletely understood. Here, we identify three conserved phosphorylation sites in NLRP3 and demonstrate that NLRP3 activation is controlled by phosphorylation of its pyrin domain (PYD)...
May 2, 2017: Journal of Experimental Medicine
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