Immune signature of patients with cardiovascular disease predicts increased risk for a severe course of COVID-19.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. So far, however, there are hardly any strategies for predicting the course of SARS-CoV-2 infection in CVD patients at hospital admission.

Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis.

Background: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown.

Methods: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement.

Immune-epithelial cell cross-talk enhances antiviral responsiveness to SARS-CoV-2 in children.

The risk of developing severe COVID-19 rises dramatically with age. Schoolchildren are significantly less likely than older people to die from SARS-CoV-2 infection, but the molecular mechanisms underlying this age-dependence are unknown. In primary infections, innate immunity is critical due to the lack of immune memory.

XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors.

Dendritic cells (DCs) are major regulators of innate and adaptive immune responses. DCs can be classified into plasmacytoid DCs and conventional DCs (cDCs) type 1 and 2. Murine and human cDC1 share the mRNA expression of XCR1.

Recovery of systemic hyperinflammation in patients with severe SARS-CoV-2 infection.

Introduction: Patients with cardiovascular disease (CVD) and acute SARS-CoV-2 infection might show an altered immune response during COVID-19.

Material And Methods: Twenty-three patients with CVD and SARS-CoV-2 infection were prospectively enrolled and received a cardiological assessment at study entry and during follow-up visit. Inclusion criteria of our study were age older than 18 years, presence of CVD, and acute SARS-CoV-2 infection.

Guidelines for mouse and human DC generation.

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non-lymphoid tissues. This article provides protocols with top ticks and pitfalls for preparation and successful generation of mouse and human DC from different cellular sources, such as murine BM and HoxB8 cells, as well as human CD34 cells from cord blood, BM, and peripheral blood or peripheral blood monocytes. We describe murine cDC1, cDC2, and pDC generation with Flt3L and the generation of BM-derived DC with GM-CSF.

Dysfunctional dendritic cells limit antigen-specific T cell response in glioma.

Background: Dendritic cells (DC), the most potent professional antigen presenting cells capable of effective cross-presentation, have been demonstrated to license T helper cells to induce antitumor immunity in solid tumors. Specific DC subtypes are recruited to the injured brain by microglial chemokines, locally adapting to distinct transcriptional profiles. In isocitrate dehydrogenase (IDH) type 1 mutant gliomas, monocyte-derived macrophages have recently been shown to display an attenuated intratumoral antigen presentation capacity as consequence of the local accumulation of the oncometabolite R-2-hydroxyglutarate.

ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury.

Platelet activation plays a critical role in thrombosis. Inhibition of platelet activation is a cornerstone in treatment of acute organ ischemia. Platelet ACKR3 surface expression is independently associated with all-cause mortality in CAD patients.

Apolipoprotein E derived from CD11c cells ameliorates atherosclerosis.

Atherosclerosis is studied in models with dysfunctional lipid homeostasis-predominantly the ApoE mouse. The role of antigen-presenting cells (APCs) for lipid homeostasis is not clear. Using a LacZ reporter mouse, we showed that CD11c cells were enriched in aortae of ApoE mice.

Sleep restriction prior to antigen exposure does not alter the T cell receptor repertoire but impairs germinal center formation during a T cell-dependent B cell response in murine spleen.

It is well known that sleep promotes immune functions. In line with this, a variety of studies in animal models and humans have shown that sleep restriction following an antigen challenge dampens the immune response on several levels which leads to e.g.

Systemic bacterial infections affect dendritic cell development and function.

Dendritic cells (DCs) are critical in host defense against infection. DC depletion is an early event in the course of sepsis that may impair the host defense mechanisms. Here, we addressed whether DC depletion and dysfunction are pathogen-independent, mediated via pattern recognition receptors, and are due to impaired DC development upon systemic infection with the Gram-negative bacterium Escherichia coli and the Gram-positive pathogen Staphylococcus aureus.

Platelet Activation and Plasma Levels of Furin Are Associated With Prognosis of Patients With Coronary Artery Disease and COVID-19.

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Numbers and phenotype of non-classical CD14dimCD16+ monocytes are predictors of adverse clinical outcome in patients with coronary artery disease and severe SARS-CoV-2 infection.

Aims: To elucidate the prognostic role of monocytes in the immune response of patients with coronary artery disease (CAD) at risk for life-threatening heart and lung injury as major complications of SARS-CoV-2 infection.

Methods And Results: From February to April 2020, we prospectively studied a cohort of 96 participants comprising 47 consecutive patients with CAD and acute SARS-CoV-2 infection (CAD + SARS-CoV-2), 19 CAD patients without infections, and 30 healthy controls. Clinical assessment included blood sampling, echocardiography, and electrocardiography within 12 h of admission.

Effects of sleep on the splenic milieu in mice and the T cell receptor repertoire recruited into a T cell dependent B cell response.

Sleep is known to improve immune function ranging from cell distribution in the naïve state to elevated antibody titers after an immune challenge. The underlying mechanisms still remain unclear, partially because most studies have focused on the analysis of blood only. Hence, we investigated the effects of sleep within the spleen in female C57BL/6J mice with normal sleep compared to short-term sleep-deprived animals both in the naïve state and after an antigen challenge.

Dendritic cell development in infection.

The immune system protects from infections primarily by detecting and eliminating invading pathogens. This is predominantly mediated by innate immune cells like neutrophils, monocytes and dendritic cells (DCs) expressing specific receptors recognizing pathogen-associated molecular patterns. DC activation by pathogens leads to the initiation of antigen-specific adaptive immune responses, thereby bridging the innate and adaptive immune systems.

Human β-Defensin 2 Mediated Immune Modulation as Treatment for Experimental Colitis.

Defensins represents an integral part of the innate immune system serving to ward off potential pathogens and to protect the intestinal barrier from microbial encroachment. In addition to their antimicrobial activities, defensins in general, and human β-defensin 2 (hBD2) in particular, also exhibit immunomodulatory capabilities. In this report, we assessed the therapeutic efficacy of systemically administered recombinant hBD2 to ameliorate intestinal inflammation in three distinct animal models of inflammatory bowel disease; i.

Sleep enhances numbers and function of monocytes and improves bacterial infection outcome in mice.

Sleep strongly impacts both humoral and cellular immunity; however, its acute effects on the innate immune defense against pathogens are unclear. Here, we elucidated in mice whether sleep affects the numbers and functions of innate immune cells and their defense against systemic bacterial infection. Sleep significantly increased numbers of classical monocytes in blood and spleen of mice that were allowed to sleep for six hours at the beginning of the normal resting phase compared to mice kept awake for the same time.

PSM Peptides From Community-Associated Methicillin-Resistant Impair the Adaptive Immune Response via Modulation of Dendritic Cell Subsets .

Dendritic cells (DCs) are key players of the immune system and thus a target for immune evasion by pathogens. We recently showed that the virulence factors phenol-soluble-modulins (PSMs) produced by community-associated methicillin-resistant (CA-MRSA) strains induce tolerogenic DCs upon Toll-like receptor activation via the p38-CREB-IL-10 pathway . Here, we addressed the hypothesis that PSMs disturb the adaptive immune response via modulation of DC subsets .

PSM Peptides Modulate Human Monocyte-Derived Dendritic Cells to Prime Regulatory T Cells.

(Sa), as one of the major human pathogens, has very effective strategies to subvert the human immune system. Virulence of the emerging community-associated methicillin-resistant Sa (CA-MRSA) depends on the secretion of phenol-soluble modulin (PSM) peptide toxins e.g.

Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine.

Endogenous circadian clocks regulate 24-h rhythms of physiology and behavior. Circadian rhythm disruption (CRD) is suggested as a risk factor for inflammatory bowel disease. However, the underlying molecular mechanisms remain unknown.

The Positron Emission Tomography Tracer 3'-Deoxy-3'-[18F]Fluorothymidine ([18F]FLT) Is Not Suitable to Detect Tissue Proliferation Induced by Systemic Yersinia enterocolitica Infection in Mice.

Most frequently, gram-negative bacterial infections in humans are caused by Enterobacteriaceae and remain a major challenge in medical diagnostics. We non-invasively imaged moderate and severe systemic Yersinia enterocolitica infections in mice using the positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), which is a marker of proliferation, and compared the in vivo results to the ex vivo biodistributions, bacterial loads, and histologies of the corresponding organs. Y.

Staphylococcus aureus PSM peptides induce tolerogenic dendritic cells upon treatment with ligands of extracellular and intracellular TLRs.

Dendritic cells (DCs) are key players of the immune system and thus a target for immune evasion by pathogens. We recently showed that the virulence factor phenol-soluble modulin (PSM) produced by community-associated methicillin-resistant Staphylococcus aureus strains induces tolerogenic DCs upon Toll-like receptor (TLR) 2 activation via the p38-CREB-IL-10 pathway. Here, we addressed the question whether this tolerogenic phenotype of DCs induced by PSMs is specific for TLR2 activation.

Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain.

Yersinia enterocolitica evades the immune response by injecting Yersinia outer proteins (Yops) into the cytosol of host cells. YopH is a tyrosine phosphatase critical for Yersinia virulence. However, the mucosal immune mechanisms subverted by YopH during in vivo orogastric infection with Y.

Mononuclear phagocytes contribute to intestinal invasion and dissemination of Yersinia enterocolitica.

Enteropathogenic Yersinia enterocolitica (Ye) enters the host via contaminated food. After colonisation of the small intestine Ye invades the Peyer's patches (PPs) via M cells and disseminates to the mesenteric lymph nodes (MLNs), spleen and liver. Whether Ye uses other invasion routes and which pathogenicity factors are required remains elusive.

New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection.

The specific and rapid detection of Enterobacteriaceae, the most frequent cause of gram-negative bacterial infections in humans, remains a major challenge. We developed a non-invasive method to rapidly detect systemic Yersinia enterocolitica infections using immunoPET (antibody-targeted positron emission tomography) with [64Cu]NODAGA-labeled Yersinia-specific polyclonal antibodies targeting the outer membrane protein YadA. In contrast to the tracer [18F]FDG, [64Cu]NODAGA-YadA uptake co-localized in a dose dependent manner with bacterial lesions of Yersinia-infected mice, as detected by magnetic resonance (MR) imaging.