scholarly journals Analysis of Th17 and Tc17 Frequencies and Antiviral Defenses in Gut-Associated Lymphoid Tissue of Chronic HIV-1 Positive Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Gabriella d’Ettorre ◽  
Giancarlo Ceccarelli ◽  
Mauro Andreotti ◽  
Carla Selvaggi ◽  
Noemi Giustini ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Lymphoid Tissue ◽  
Cell Activation ◽  
Immune Cell ◽  
Effector Memory ◽  
Type I ◽  
Type I Ifn ◽  
Immune Cell Activation ◽  
Blood Compartment ◽  
Hiv 1

The complex relationship between both the Th1/Th17 and Tc1/Tc17 axis and innate defences in the intestinal mucosa during HIV-1 infection has not been well characterized. This study examined the frequency, phenotype, and functional status of T cell populations in the gut-associated lymphoid tissue and peripheral blood of virologically suppressed HIV-1-infected patients on therapy, focusing on the Th1, Th17, Tc1, and Tc17 cell subsets. We found a persistent immune cell activation (CD38 and HLADR expression) into the GALT despite the higher levels of Th17 and Tc17 in respect to peripheral blood. An upregulation of type I IFN response in GALT compared to the peripheral blood compartment was also recorded. Furthermore, IFN-α/βlevels were negatively related to the frequencies of Th1 naïve cells and Tc1 cell subsets (naïve, central memory, and effector memory) in the GALT. In contrast, no relationships between type I IFN response and Th1 or Tc1 cell subsets in peripheral blood compartment and between IFN-α/βand Th17/Tc17 in both GALT and peripheral blood district were recorded. These data indicate that prolonged antiretroviral treatment improves GALT immune function despite the persistence of immune activation and type I IFN response in chronic HIV-1 positive patients.

scholarly journals A combination of Interferon Stimulated Genes is more effective than IFNα and IFNβ in reducing HIV-1 replication in human cervicovaginal tissues

2019 ◽  
Author(s):  
Christiane Rollenhagen ◽  
Jiang Gui ◽  
Gustavo F. Doncel ◽  
Susana N. Asin
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Experimental Models ◽  
Heterosexual Transmission ◽  
Inflammatory Factors ◽  
Type I ◽  
Interferon Stimulated Genes ◽  
Immune Cell Activation ◽  
Molecular Pattern ◽  
Hiv 1

AbstractEnhancing antiviral responses while controlling immune cell activation is an attractive strategy to reduce HIV-1 replication in the cervicovaginal mucosae, a primary site of heterosexual transmission. Interferon alpha and beta (IFNα/β) signaling up-regulates expression of inflammatory factors and Interferon-Stimulated Genes (ISGs). The simultaneous induction of both IFNs by pathogen-bound molecular pattern recognition receptors and the paucity of data on the anti-HIV-1 efficacy of a combination of these antiviral factors or their downstream targets in human experimental models taking into account mucosal and submucosal cell populations, motivated us to determine whether combined IFNα/β or ISGs could decrease HIV-1 replication in cervicovaginal tissues.IFNα/β reduced HIV-1 p24 release. This reduction was associated with upregulation of expression of a subset of ISGs, the type I IFN receptor and interferon regulatory factor seven. IFNα/β also enhanced immune cell activation. In contrast, when added directly to CV tissues, a combination of ISGs was more effective than IFNα/β in reducing HIV-1 p24 release. The ISG combination demonstrated early kinetics and a more robust reduction in HIV-1 p24 release. Opposite to IFNα/β, the combination of ISGs did not induce immune cell activation.IFNα/β-induced ISGs provide novel mucosal therapeutic targets with a greater capacity to reduce HIV-1 compared to IFNα/β, without inducing immune cell activation.

Antibody Inhibition of HIV-1 Transmission from Antigen-presenting Cells to CD4 T Lymphocytes Involves Immune Cell Activation

2014 ◽  
Vol 30 (S1) ◽  
pp. A154-A154
Author(s):  
Bin Su ◽  
Alexandre Lederle ◽  
Géraldine Laumond ◽  
Sylvie Schmidt ◽  
Thomas Decoville ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cell Activation ◽  
Immune Cell ◽  
Antigen Presenting Cells ◽  
Immune Cell Activation ◽  
Antigen Presenting ◽  
Antibody Inhibition ◽  
Hiv 1

scholarly journals Acquired resistance to PD-L1 inhibition is associated with an enhanced type I IFN-stimulated secretory program in tumor cells

2021 ◽  
Author(s):  
Yuhao Shi ◽  
Melissa Dolan ◽  
Michalis Mastri ◽  
James W. Hill ◽  
Adam Dommer ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Immune Cell ◽  
Ex Vivo ◽  
Gene Knockout ◽  
Acquired Resistance ◽  
Mouse Tumor ◽  
Type I ◽  
Type I Ifn ◽  
Signaling Crosstalk

Therapeutic inhibition of programmed cell death ligand (PD-L1) can reverse PD-1-mediated suppression of tumor-killing T-cells; however, many patients develop resistance. Acquired resistance may be derived from intracellular PD-L1 and interferon (IFN) signaling programs in the tumor that can have dual, sometimes opposing, influences on tumor immune responses. Here we show that PD-L1 inhibition induces a novel secretory program tightly controlled by IFN-signaling and specific to acquired, but not innate, resistance in tumors. A PD-L1 treatment-induced secretome (PTIS) was found to be enriched for several IFN-stimulated genes (ISGs) and then further enhanced by type I IFN stimulation (IFNα or IFNβ) in multiple mouse tumor models. Chronic inhibition or gene knockout of tumor PD-L1 in vitro could elicit similar type I IFN-enhanced secretory stimulation while resistant cells were able to suppress T cell activation and killing ex vivo. When reimplanted into mice, resistant tumors were more sensitive to IL-6 inhibition (a key PTIS component) and growth significantly reduced when type I IFN signaling was blocked. Together, these results show that prolonged PD-L1 inhibition can 'rewire' existing intracellular IFN:PD-L1 signaling crosstalk to drive secretory programs that help protect tumors from immune cell attack and represent a targetable vulnerability to overcome acquired resistance in patients.

scholarly journals Analysis of type I IFN response and T cell activation in severe COVID-19/HIV-1 coinfection

Medicine ◽  
2020 ◽  
Vol 99 (36) ◽  
pp. e21803 ◽  
Author(s):  
Gabriella d’Ettorre ◽  
Gregorio Recchia ◽  
Marco Ridolfi ◽  
Guido Siccardi ◽  
Claudia Pinacchio ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Type I ◽  
Type I Ifn ◽  
Hiv 1

The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps

2021 ◽  
Vol 14 (673) ◽  
pp. eaax7942
Author(s):  
Falko Apel ◽  
Liudmila Andreeva ◽  
Lorenz Sebastian Knackstedt ◽  
Robert Streeck ◽  
Christian Karl Frese ◽  
...  
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Myeloid Cells ◽  
Neutrophil Extracellular Traps ◽  
Type I Interferons ◽  
Type I ◽  
Immune Cell Activation ◽  
Extracellular Traps ◽  
Regulated Cell Death

Neutrophil extracellular traps (NETs) are structures consisting of chromatin and antimicrobial molecules that are released by neutrophils during a form of regulated cell death called NETosis. NETs trap invading pathogens, promote coagulation, and activate myeloid cells to produce type I interferons (IFNs), proinflammatory cytokines that regulate the immune system. Here, we showed that macrophages and other myeloid cells phagocytosed NETs. Once in phagosomes, NETs translocated to the cytosol, where the DNA backbones of these structures activated the innate immune sensor cyclic GMP-AMP synthase (cGAS) and induced type I IFN production. The NET-associated serine protease neutrophil elastase (NE) mediated the activation of this pathway. We showed that NET induction in mice treated with the lectin concanavalin A, a model of autoimmune hepatitis, resulted in cGAS-dependent stimulation of an IFN response, suggesting that NETs activated cGAS in vivo. Thus, our findings suggest that cGAS is a sensor of NETs, mediating immune cell activation during infection.

Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis

2013 ◽  
Vol 20 (37) ◽  
pp. 4806-4814 ◽  
Author(s):  
Brigitta Buttari ◽  
Elisabetta Profumo ◽  
Rita Businaro ◽  
Luciano Saso ◽  
Raffaele Capoano ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Cell Activation ◽  
Immune Cell ◽  
Therapeutic Targets ◽  
Immune Cell Activation ◽  
Novel Therapeutic

scholarly journals Neuronal guidance proteins in cardiovascular inflammation

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Marius Keller ◽  
Valbona Mirakaj ◽  
Michael Koeppen ◽  
Peter Rosenberger
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Vascular Endothelial ◽  
Therapeutic Approaches ◽  
Immune Cell Activation ◽  
Cytokines And Chemokines ◽  
The Future ◽  
Cardiovascular Pathologies ◽  
Neuronal Guidance

AbstractCardiovascular pathologies are often induced by inflammation. The associated changes in the inflammatory response influence vascular endothelial biology; they complicate the extent of ischaemia and reperfusion injury, direct the migration of immune competent cells and activate platelets. The initiation and progression of inflammation is regulated by the classical paradigm through the system of cytokines and chemokines. Therapeutic approaches have previously used this knowledge to control the extent of cardiovascular changes with varying degrees of success. Neuronal guidance proteins (NGPs) have emerged in recent years and have been shown to be significantly involved in the control of tissue inflammation and the mechanisms of immune cell activation. Therefore, proteins of this class might be used in the future as targets to control the extent of inflammation in the cardiovascular system. In this review, we describe the role of NGPs during cardiovascular inflammation and highlight potential therapeutic options that could be explored in the future.

scholarly journals Oxidative stress and immune cell activation quantification in sepsis and non-sepsis critical care patients by neopterin/7,8-dihydroneopterin analysis

Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 68-82
Author(s):  
Gregory Baxter-Parker ◽  
Ravinder Reddy Gaddam ◽  
Elena Moltchanova ◽  
Anitra Carr ◽  
Geoff Shaw ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Function ◽  
Cell Activation ◽  
Immune Cell ◽  
Intensive Care Patients ◽  
Immune Cell Activation ◽  
Immune System Activation ◽  
System Activation ◽  
Urinary Neopterin ◽  
Critical Care Patients

AbstractIntroduction: Neopterin and 7,8-dihydroneopterin are used as biomarkers of oxidative stress and inflammation, but the effect of kidney function on these measurements has not been extensively explored. We examine the levels of oxidative stress, inflammation and kidney function in intensive patients and compare them to equivalent patients without sepsis.Methods: 34 Intensive care patients were selected for the study, 14 without sepsis and 20 with. Both groups had equivalent levels of trauma, assessed by SAPS II, SOFA, and APACHE II and III scores. Plasma and urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) values were measured.Results: Neopterin and total neopterin were significantly elevated in urine and plasma for multiple days in sepsis versus non-sepsis patients. Plasma neopterin and total neopterin have decreasing relationships with increased eGFR (p<0.008 and p<0.001, respectively). Plasma/urinary neopterin and total neopterin ratios demonstrate that total neopterin flux is more influenced by eGFR than neopterin, with significantce of p<0.02 and p<0.0002 respectively.Conclusion: Sepsis patients present with greater levels of oxidative stress and immune system activation than non-sepsis patients of equal levels of trauma, as measured by neopterin and total neopterin. eGFR may need to be taken into account when accessing the level of inflammation from urinary neopterin measurements.

scholarly journals RhoA Signaling in Immune Cell Response and Cardiac Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1681
Author(s):  
Lucia Sophie Kilian ◽  
Derk Frank ◽  
Ashraf Yusuf Rangrez
Keyword(s):  
Cardiac Disease ◽  
Cell Response ◽  
Cell Activation ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Heart Diseases ◽  
Small Gtpase ◽  
Cardiac Inflammation ◽  
Immune Cell Activation ◽  
Immune Cell Response

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spiral down to immune cell activation and chronic state of low-level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

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