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Innate memory

Aida S Hansen, Bettina B Bundgaard, Bjarne K Møller, Per Höllsberg
CD46 is a glycoprotein with important functions in innate and adaptive immune responses. Functionally different isoforms are generated by alternative splicing at exons 7-9 (BC and C isoforms) and exon 13 (CYT-1 and CYT-2 isoforms) giving rise to BC1, BC2, C1 and C2. We developed a novel real-time PCR assay that allows quantitative comparisons between these isoforms. Their relative frequency in CD4(+) T cells from 100 donors revealed a distribution with high interpersonally variability. Importantly, the distribution between the isoforms was not random and although splicing favoured inclusion of exon 8 (BC isoforms), exclusion of exon 8 (C isoforms) was significantly linked to exclusion of exon 13 (CYT-2 isoforms)...
October 14, 2016: Scientific Reports
Leticia Ramírez-Lugo, Ana Peñas-Rincón, Sandybel Ángeles-Durán, Francisco Sotres-Bayon
: The ability to select an appropriate behavioral response guided by previous emotional experiences is critical for survival. Although much is known about brain mechanisms underlying emotional associations, little is known about how these associations guide behavior when several choices are available. To address this, we performed local pharmacological inactivations of several cortical regions before retrieval of an aversive memory in choice-based versus no-choice-based conditioned taste aversion (CTA) tasks in rats...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Siroon Bekkering, Bastiaan A Blok, Leo A B Joosten, Niels P Riksen, Reinout van Crevel, Mihai G Netea
BACKGROUND: Innate immune memory or 'trained immunity' has recently been described as an important property of cells of the innate immune system. Due to the increased interest in this important new field of immunological investigation we sought to determine the optimal conditions for an in-vitro experimental protocol of monocyte training using three of the most commonly used training stimuli from the literature: β-glucan, the Bacille Calmette-Guérin (BCG) vaccine, and oxidized LDL (oxLDL)...
October 12, 2016: Clinical and Vaccine Immunology: CVI
Lexus R Johnson, Orr-El Weizman, Moritz Rapp, Sing Sing Way, Joseph C Sun
Despite robust secondary T cell expansion primed by vaccination, the impact on primary immune responses to heterotypic antigens remains undefined. Here we show that secondary expansion of epitope-specific memory CD8(+) T cells primed by prior infection with recombinant pathogens limits the primary expansion of naive CD8(+) T cells with specificity to new heterologous antigens, dampening protective immunity against subsequent pathogen challenge. The degree of naive T cell repression directly paralleled the magnitude of the recall response...
October 11, 2016: Cell Reports
Rob J W Arts, Mihai G Netea
The innate immune system is considered to have no immune memory. However, lately there has been as shift in paradigm. Cells of the innate immune system, and especially monocytes and macrophages, are capable of building a nonspecific memory, resulting in either better or worse responses to secondary stimulations/infections, as a result of epigenetic changes. This review gives a general overview of the at-the-moment available data.
August 2016: Microbiology Spectrum
Yujing Bi
As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial "noninflammatory" phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called "proinflammatory" phase...
2016: Advances in Experimental Medicine and Biology
René H M Raeven, Jolanda Brummelman, Larissa van der Maas, Wichard Tilstra, Jeroen L A Pennings, Wanda G H Han, Cécile A C M van Els, Elly van Riet, Gideon F A Kersten, Bernard Metz
Effective immunity against Bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. Natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. We applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotected mice and protected mice with infection-induced immunity, around a B...
2016: PloS One
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Hye-Soo Park, Hyun Shik Bae, Chul Hee Choi, Hwa-Jung Kim
Macrophages constitute the first line of defense against Mycobacterium tuberculosis and are critical in linking innate and adaptive immunity. Therefore, the identification and characterization of mycobacterial proteins that modulate macrophage function are essential for understanding tuberculosis pathogenesis. In this study, we identified the novel macrophage-activating protein, Rv2882c, from M. tuberculosis culture filtrate proteins. Recombinant Rv2882c protein activated macrophages to secrete pro-inflammatory cytokines and express co-stimulatory and major histocompatibility complex molecules via Toll-like receptor 4, myeloid differentiation primary response protein 88, and Toll/IL-1 receptor-domain-containing adaptor inducing IFN-beta...
2016: PloS One
Natascha Luther, Fatemeh Shahneh, Melanie Brähler, Franziska Krebs, Sven Jäckel, Saravanan Subramaniam, Christian Stanger, Tanja Schönfelder, Bettina Kleis-Fischer, Christoph Reinhardt, Hans C Probst, Philip Wenzel, Katrin Schäfer, Christian Becker
RATIONALE: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and non-immune cell function, however their role in sterile inflammation in venous thrombosis has not been systematically examined. OBJECTIVE: This study investigated the recruitment, activation and inflammatory activity of T cells in deep vein thrombosis (DVT) and its consequences for venous thrombus resolution. METHODS AND RESULTS: CD4(+) and CD8(+) T cells infiltrate the thrombus and vein wall rapidly upon DVT induction and remain in the tissue throughout thrombus resolution...
October 5, 2016: Circulation Research
María Del Mar Valenzuela-Membrives, Francisco Perea-García, Abel Sanchez-Palencia, Francisco Ruiz-Cabello, Mercedes Gómez-Morales, María Teresa Miranda-León, Inmaculada Galindo-Angel, María Esther Fárez-Vidal
Immune cell infiltration is a common feature of many human solid tumors. Innate and adaptative immune systems contribute to tumor immunosurveillance. We investigated whether tumors evade immune surveillance by inducing states of tolerance and/or through the inability of some immune subpopulations to effectively penetrate tumor nests. Immunohistochemistry and flow cytometry analysis were used to study the composition and distribution of immune subpopulations in samples of peripheral blood, tumor tissue (TT), adjacent tumor tissue (ATT), distant non-tumor tissue (DNTT), cancer nests, cancer stroma, and invasive margin in 61 non-small-cell lung cancer (NSCLC) patients...
September 26, 2016: Oncotarget
Rob J W Arts, Leo A B Joosten, Mihai G Netea
The classical view that only adaptive immunity can build immunological memory has recently been challenged. Both in organisms lacking adaptive immunity as well as in mammals, the innate immune system can adapt to mount an increased resistance to reinfection, a de facto innate immune memory termed trained immunity. Recent studies have revealed that rewiring of cellular metabolism induced by different immunological signals is a crucial step for determining the epigenetic changes underlying trained immunity. Processes such as a shift of glucose metabolism from oxidative phosphorylation to aerobic glycolysis, increased glutamine metabolism and cholesterol synthesis, play a crucial role in these processes...
September 26, 2016: Seminars in Immunology
Amanda K Huber, David A Giles, Benjamin M Segal, David N Irani
Eotaxins are C-C motif chemokines first identified as potent eosinophil chemoattractants. They facilitate eosinophil recruitment to sites of inflammation in response to parasitic infections as well as allergic and autoimmune diseases such as asthma, atopic dermatitis, and inflammatory bowel disease. The eotaxin family currently includes three members: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26). Despite having only ~30% sequence homology to one another, each was identified based on its ability to bind the chemokine receptor, CCR3...
September 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Jong-Chan Youn
Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and T cell immunosenescence especially...
September 2016: Journal of Hypertension
Trevor Hardigan, Rebecca Ward, Adviye Ergul
The incidence of diabetes has more than doubled in the United States in the last 30 years and the global disease rate is projected to double by 2030. Cognitive impairment has been associated with diabetes, worsening quality of life in patients. The structural and functional interaction of neurons with the surrounding vasculature is critical for proper function of the central nervous system including domains involved in learning and memory. Thus, in this review we explore cognitive impairment in patients and experimental models, focusing on links to vascular dysfunction and structural changes...
October 1, 2016: Clinical Science (1979-)
Bianca A Silva, Cornelius T Gross, Johannes Gräff
How fear is represented in the brain has generated a lot of research attention, not only because fear increases the chances for survival when appropriately expressed but also because it can lead to anxiety and stress-related disorders when inadequately processed. In this review, we summarize recent progress in the understanding of the neural circuits processing innate fear in rodents. We propose that these circuits are contained within three main functional units in the brain: a detection unit, responsible for gathering sensory information signaling the presence of a threat; an integration unit, responsible for incorporating the various sensory information and recruiting downstream effectors; and an output unit, in charge of initiating appropriate bodily and behavioral responses to the threatful stimulus...
October 2016: Learning & Memory
Ana Villegas-Mendez, Colette A Inkson, Tovah N Shaw, Patrick Strangward, Kevin N Couper
CD4(+) T cells that produce IFN-γ are the source of host-protective IL-10 during primary infection with a number of different pathogens, including Plasmodium spp. The fate of these CD4(+)IFN-γ(+)IL-10(+) T cells following clearance of primary infection and their subsequent influence on the course of repeated infections is, however, presently unknown. In this study, utilizing IFN-γ-yellow fluorescent protein (YFP) and IL-10-GFP dual reporter mice, we show that primary malaria infection-induced CD4(+)YFP(+)GFP(+) T cells have limited memory potential, do not stably express IL-10, and are disproportionately lost from the Ag-experienced CD4(+) T cell memory population during the maintenance phase postinfection...
September 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Emma L Culver, Roger W Chapman
IgG4-related hepatobiliary diseases are part of a multiorgan fibroinflammatory condition termed IgG4-related disease, and include IgG4-related sclerosing cholangitis (IgG4-SC) and IgG4-related hepatopathy. These diseases can present with biliary strictures and/or mass lesions, making them difficult to differentiate from primary sclerosing cholangitis (PSC) or other hepatobiliary malignancies. Diagnosis is based on a combination of clinical, biochemical, radiological and histological findings. However, a gold standard diagnostic test is lacking, warranting the identification of more specific disease markers...
October 2016: Nature Reviews. Gastroenterology & Hepatology
Valentina Perri, Elena Gianchecchi, Riccardo Scarpa, Mariella Valenzise, Maria Manuela Rosado, Ezio Giorda, Antonino Crinò, Marco Cappa, Susi Barollo, Silvia Garelli, Corrado Betterle, Alessandra Fierabracci
APECED is a T-cell mediated disease with increased frequencies of CD8+ effector and reduction of FoxP3+ T regulatory cells. Antibodies against affected organs and neutralizing to cytokines are found in the peripheral blood. The contribution of B cells to multiorgan autoimmunity in Aire-/- mice was reported opening perspectives on the utility of anti-B cell therapy. We aimed to analyse the B cell phenotype of APECED patients compared to age-matched controls. FACS analysis was conducted on PBMC in basal conditions and following CpG stimulation...
September 9, 2016: Immunobiology
Robert Zeiser, Gerard Socié, Bruce R Blazar
Acute graft-versus-host disease (aGVHD) is a major life-threatening complication of allogeneic haematopoietic cell transplantation (allo-HCT). Here we discuss the aGVHD pathophysiology initiated by multiple signals that cause alloreactive T-cell activation. The outcome of such donor T-cell activation is influenced by T-cell receptor-signal strength, anatomical location, co-stimulatory/co-inhibitory signals and differentiation stage (naive, effector/memory) of T-cells. Additionally, cross-priming of T cells to antigens expressed by pathogens can contribute to aGVHD-mediated tissue injury...
October 2016: British Journal of Haematology
Katia Falasca, Marcella Reale, Claudio Ucciferri, Marta Di Nicola, Giuseppe Di Martino, Chiara D'Angelo, Simona Coladonato, Jacopo Vecchiet
The HIV may trigger a process of neuronal loss and axonal degeneration throughout the brain, which is carried on by the immune system releasing of proinflammatory cytokines, so that chronic inflammation associated with dysregulated innate immune response, glial cell dysfunction, and adverse antiretroviral therapy (ART) effect play an important role causing milder HIV-associated neurocognitive disorders or asymptomatic neurocognitive impairment. All patients have been tested for neurocognitive functioning through a comprehensive, five-domain neuropsychological battery performed in the study...
October 12, 2016: AIDS Research and Human Retroviruses
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