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Danger signal

Moritz Peiseler, Paul Kubes
Severe trauma is accompanied by a profound activation of the immune system. Patients with polytrauma develop systemic inflammatory response syndrome (SIRS) and often sepsis, which contributes substantially to high mortality of this condition. On a cellular level, necrosis and loss of plasma membrane integrity lead to the release of endogenous "damage-associated molecular patterns" (DAMPs) as danger signals, which in turn activate innate immune cells. Inflammation that occurs in the absence of invading pathogens has been termed sterile inflammation and trauma with tissue damage represents an acute form of sterile inflammation...
April 17, 2018: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
Ralf Küppers, Freda K Stevenson
The development of follicular lymphoma (FL) from a founder B cell with an upregulation of BCL2, via the t(14;18) translocation, to a proliferating clone, poised to undergo further transformation to an aggressive lymphoma, illustrates the opportunistic Darwinian process of tumorigenesis. Protection against apoptosis allows an innocent cell to persist and divide, with dangerous accumulation of further mutational changes, commonly involving inactivation of chromatin-modifying genes. But this is not all. FL cells reflect normal B cells in relying on expression of surface Ig...
April 17, 2018: Blood
Joanne K Gardner, Scott M J Cornwall, Arthur W Musk, John Alvarez, Cyril D S Mamotte, Connie Jackaman, Anna K Nowak, Delia J Nelson
There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m)DC1s, mDC2s, plasmacytoid (p)DCs, and monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years) healthy human volunteers to LPS/IFN-γ or CD40L stimulation...
2018: PloS One
Djo Hasan, Joshua Satalin, Philip van der Zee, Michaela Kollisch-Singule, Paul Blankman, Atsuko Shono, Peter Somhorst, Corstiaan den Uil, Han Meeder, Toru Kotani, Gary F Nieman
Stretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases...
April 13, 2018: International Journal of Molecular Sciences
Christina Mehrfeld, Steven Zenner, Miroslaw Kornek, Veronika Lukacs-Kornek
The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical location, it is constantly exposed to microbial and food-derived antigens from the gut and thus equipped with a complex cellular network that ensures dampening T-cell responses. Within this cellular network, parenchymal cells (hepatocytes), non-parenchymal cells (liver sinusoidal endothelial cells and hepatic stellate cells), and immune cells contribute directly or indirectly to this process. Despite this refractory bias, the liver is capable of mounting efficient T-cell responses...
2018: Frontiers in Immunology
Shannon M Wallet, Vishwajeet Puri, Frank C Gibson
Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) that provide innate immune sensing of conserved pathogen-associated molecular patterns (PAMPs) to engage early immune recognition of bacteria, viruses, and protozoa. Furthermore, TLRs provide a conduit for initiation of non-infectious inflammation following the sensing of danger-associated molecular patterns (DAMPs) generated as a consequence of cellular injury. Due to their essential role as DAMP and PAMP sensors, TLR signaling also contributes importantly to several systemic diseases including cardiovascular disease, diabetes, and others...
April 5, 2018: Vaccines
Michael H Kogut, Kenneth J Genovese, Christina L Swaggerty, Haiqi He, Leon Broom
The intestinal tract harbors a diverse community of microbes that have co-evolved with the host immune system. Although many of these microbes execute functions that are critical for host physiology, the host immune system must control the microbial community so that the dynamics of this interdependent relationship is maintained. To facilitate host homeostasis, the immune system ensures that the microbial load is tolerated, but anatomically contained, while remaining reactive to microbial invasion. Inflammation is the most prevalent manifestation of host defense in reaction to alterations in tissue homeostasis and is elicited by innate immune receptors that recognize and detect infection, host damage, and danger signaling molecules that activate a highly regulated network of immunological and physiological events for the purpose of maintaining homeostasis and restoring functionality...
March 30, 2018: Poultry Science
William G Fusco, Joseph A Duncan
Inflammasomes are multiprotein structures that activate caspase-1, support secretion of pro-inflammatory cytokines, IL-1β and IL-18, and also induce inflammatory programmed cell death, termed pyoptosis. Inflammasomes are activated in response to the detection of endogenous and microbially derived danger signals and are mediated by several classes of inflammasome-forming sensors. These include several nucleotide-binding proteins of the NOD-like receptor (NLR) family, including NLRP1, NLRP3 and NLRC4, as well as the proteins Absent in Melanoma 2 (AIM2) and Pyrin...
February 14, 2018: International Immunology
Elisabeth Zechendorf, Phillip Vaßen, Jieyi Zhang, Ahmed Hallawa, Antons Martincuks, Oliver Krenkel, Gerhard Müller-Newen, Tobias Schuerholz, Tim-Philipp Simon, Gernot Marx, Gerd Ascheid, Anke Schmeink, Guido Dartmann, Christoph Thiemermann, Lukas Martin
Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes...
2018: Frontiers in Immunology
Rui Wu, Yuhong Zhang, Yu Xiang, Yishu Tang, Fang Cui, Ju Cao, Lan Zhou, Yan You, Liang Duan
BACKGROUND: S100A9 protein, which is recently classified as a novel damage associated molecular pattern, is released from stressed cells undergoing necrosis or secreted by living cells undergoing a stress that act as endogenous danger signal associated with infection, tissue damage and cancer. Here, we evaluated the relationship of serum S100A9 with viral replication and liver necroinflammation in patients with chronic hepatitis B (CHB) infection. METHODS: A total of one hundred and eighty-three recruited patients with CHB infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S)...
April 3, 2018: Journal of Translational Medicine
Thomas Vogl, Athanasios Stratis, Viktor Wixler, Tom Völler, Sumita Thurainayagam, Selina K Jorch, Stefanie Zenker, Alena Dreiling, Deblina Chakraborty, Mareike Fröhling, Peter Paruzel, Corinna Wehmeyer, Sven Hermann, Olympia Papantonopoulou, Christiane Geyer, Karin Loser, Michael Schäfers, Stephan Ludwig, Monika Stoll, Tomas Leanderson, Joachim L Schultze, Simone König, Thomas Pap, Johannes Roth
Autoimmune diseases, such as psoriasis and arthritis, show a patchy distribution of inflammation despite systemic dysregulation of adaptive immunity. Thus, additional tissue-derived signals, such as danger-associated molecular patterns (DAMPs), are indispensable for manifestation of local inflammation. S100A8/S100A9 complexes are the most abundant DAMPs in many autoimmune diseases. However, regulatory mechanisms locally restricting DAMP activities are barely understood. We now unravel for the first time, to our knowledge, a mechanism of autoinhibition in mice and humans restricting S100-DAMP activity to local sites of inflammation...
April 3, 2018: Journal of Clinical Investigation
Mary C Sarlitto, Allison R Foilb, John P Christianson
Survival depends on adaptation to shiftingenvironmentalrisks and opportunities.Regarding risks, the mechanisms which permit acquisition, recall, and flexible use of aversive associations is poorly understood. Drawing on the evidence that the orbital frontal cortex is critical to integrating outcome expectancies with flexible appetitive behavioral responses, we hypothesized that OFC would contribute to behavioral flexibility within an aversive learning domain. We introduce a fear conditioning procedure in which adult male rats were presented with shock-paired conditioned stimulus (CS+) or a safety cue (CS-)...
March 28, 2018: Neuroscience
Eric I Elliott, Alexis N Miller, Balaji Banoth, Shankar S Iyer, Aleksandr Stotland, Jerrold P Weiss, Roberta A Gottlieb, Fayyaz S Sutterwala, Suzanne L Cassel
The NLRP3 inflammasome is activated in response to microbial and danger signals, resulting in caspase-1-dependent secretion of the proinflammatory cytokines IL-1β and IL-18. Canonical NLRP3 inflammasome activation is a two-step process requiring both priming and activation signals. During inflammasome activation, NLRP3 associates with mitochondria; however, the role for this interaction is unclear. In this article, we show that mouse NLRP3 and caspase-1 independently interact with the mitochondrial lipid cardiolipin, which is externalized to the outer mitochondrial membrane at priming in response to reactive oxygen species...
March 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Anna Dubaniewicz
In the light of modified the Matzinger's model of immune response, human heat shock proteins (hsp) as main "danger signals" tissue damage-associated molecular patterns (DAMPs) or/and microbial hsp as pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid granuloma by both infectious and non-infectious factors in genetically different predisposed host. Regarding infectious causes of sarcoid models, low-virulence strains of, e.g. mycobacteria and propionibacteria recognized through genetically changed PRR and persisting in genetically altered host phagocytes, generate increased release of both human and microbial hsp with their molecular and functional homology...
March 27, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Anna Dubaniewicz
In the light of modified the Matzinger's model of immune response, human heat shock proteins (hsp) as main 'danger signals' (tissue damage-associated molecular patterns-DAMPs) or/and microbial hsp as pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid granuloma by both infectious and non-infectious factors in genetically different predisposed host.
March 27, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Alexandre Presas, David Valentin, Mònica Egusquiza, Carme Valero, Eduard Egusquiza
Hydropower plants are of paramount importance for the integration of intermittent renewable energy sources in the power grid. In order to match the energy generated and consumed, Large hydraulic turbines have to work under off-design conditions, which may lead to dangerous unstable operating points involving the hydraulic, mechanical and electrical system. Under these conditions, the stability of the grid and the safety of the power plant itself can be compromised. For many Francis Turbines one of these critical points, that usually limits the maximum output power, is the full load instability...
March 30, 2018: Sensors
Daniel Rojas-Sepúlveda, Andrés Tittarelli, María Alejandra Gleisner, Ignacio Ávalos, Cristián Pereda, Iván Gallegos, Fermín Eduardo González, Mercedes Natalia López, Jean Michel Butte, Juan Carlos Roa, Paula Fluxá, Flavio Salazar-Onfray
Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials...
March 29, 2018: Cancer Immunology, Immunotherapy: CII
Manuela Minguzzi, Silvia Cetrullo, Stefania D'Adamo, Ylenia Silvestri, Flavio Flamigni, Rosa Maria Borzì
The prevalence of Osteoarthritis (OA) is increasing because of the progressive aging and unhealthy lifestyle. These risk factors trigger OA by removing constraints that keep the tightly regulated low turnover of the extracellular matrix (ECM) of articular cartilage, the correct chondrocyte phenotype, and the functionality of major homeostatic mechanisms, such as mitophagy, that allows for the clearance of dysfunctional mitochondria, preventing increased production of reactive oxygen species, oxidative stress, and senescence...
2018: Oxidative Medicine and Cellular Longevity
Christine Tucher, Konrad Bode, Petra Schiller, Laura Claßen, Carolin Birr, Maria Margarida Souto-Carneiro, Norbert Blank, Hanns-Martin Lorenz, Martin Schiller
Extracellular vesicles (EVs) are released from nearly all mammalian cells and different EV populations have been described. Microvesicles represent large EVs (LEVs) released from the cellular surface, while exosomes are small EVs (SEVs) released from an intracellular compartment. As it is likely that different stimuli promote the release of distinct EV populations, we analyzed EVs from human lymphocytes considering the respective release stimuli (activation Vs. apoptosis induction). We could clearly separate two EV populations, namely SEVs (average diameter <200 nm) and LEVs (diameter range between 200 and 1000 nm)...
2018: Frontiers in Immunology
Thomas Wieder, Thomas Eigentler, Ellen Brenner, Dipl Biol, Martin Röcken
Immune checkpoints are accessory molecules that either promote or inhibit T cell activation. Two inhibitory molecules, cytotoxic T cell antigen 4 (CTLA-4) and programmed death 1 (PD-1), got high attention, as inhibition of CTLA-4 or PD-1 signaling provides the first immune therapy that significantly improves the survival of patients with metastatic solid cancers. Inhibition of CTLA-4 or PD-1 was first studied in and approved for patients with metastatic melanoma. Blocking immune checkpoints is also efficient in non-small-cell lung cancer, renal cell cancers, hypermutated gastro-intestinal cancers and others...
March 26, 2018: Journal of Allergy and Clinical Immunology
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