C-C Motif Ligand 7 (CCL7) and C-C Motif Chemokine Receptor 3 (CCR3) dysregulation in patients with scrub typhus and association with mortality.

Background: Scrub typhus, caused by Orientia tsutsugamushi involves infiltration of a mixture of perivascular lymphocytes and macrophages into affected organs. We investigated if this is characterized by chemokine dysregulation.

Methods: mRNA expression of chemokines and receptors were screened in whole blood by cDNA microarray in a subgroup of patients and controls.

Canonical notch activation in patients with scrub typhus: association with organ dysfunction and poor outcome.

Purpose: The mechanisms that control inflammation in scrub typhus are not fully elucidated. The Notch pathways are important regulators of inflammation and infection, but have not been investigated in scrub typhus.

Methods: Plasma levels of the canonical Notch ligand Delta-like protein 1 (DLL1) were measured by enzyme immunoassay and RNA expression of the Notch receptors (NOTCH1, NOTCH2 and NOTCH4) in whole blood was analyzed by real-time PCR in patients with scrub typhus (n = 129), in patients with similar febrile illness without O.

Cholangiocytes Modulate CD100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation.

Background & Aims: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms.

Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue.

Background: Epstein-Barr virus (EBV) causes infectious mononucleosis (IM) that can lead to chronic fatigue syndrome. The CEBA-project (Chronic fatigue following acute EBV infection in Adolescents) has followed 200 patients with IM and here we present an immunological profiling of adolescents with IM related to clinical characteristics.

Methods: Patients were sampled within 6 weeks of debut of symptoms and after 6 months.

IL-18 and IL-18 binding protein are related to disease severity and parasitemia during falciparum malaria.

Background: Several inflammatory molecules participate in the immune response to malaria. Interleukin (IL)-18 is an inflammatory cytokine activated by NLRP3 inflammasomes. In clinical falciparum malaria, with and without HIV co-infection, data on IL-18 and in particular on its binding protein, IL-18bp, is scarce.

Secreted Wnt antagonists in scrub typhus.

Background: The mechanisms that control local and systemic inflammation in scrub typhus have only been partially elucidated. The wingless (Wnt) signaling pathways are emerging as important regulators of inflammation and infection, but have not been investigated in scrub typhus.

Methodology/principal Findings: Plasma levels of secreted Wnt antagonists (i.

Gut Microbiota-Dependent Trimethylamine N-Oxide Associates With Inflammation in Common Variable Immunodeficiency.

A substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has hitherto not been investigated in relation to CVID.

Plasma parasitemia as assessed by quantitative PCR in relation to clinical disease severity in African adults with falciparum malaria with and without HIV co-infection.

Purpose: When considering malaria disease severity, estimation of parasitemia in erythrocytes is important, but sometimes misleading, since the infected erythrocytes may be sequestered in peripheral capillaries. In African children and Asian adults with falciparum malaria, parasitemia as assessed by quantitative PCR (qPCR) in plasma seems to be a valuable indicator of disease severity, but data on African adults as well as the impact of co-infection with HIV is lacking.

Methods: In 131 patients with falciparum malaria in a public tertiary teaching hospital in Mozambique, plasma malaria parasitemia as assessed by qPCR, compared to qualitative malaria PCR in blood cell fraction, was related to malaria disease severity and HIV co-infection.

Plasma levels of interleukin 27 in falciparum malaria is increased independently of co-infection with HIV: potential immune-regulatory role during malaria.

Background: The immune response during falciparum malaria mediates both harmful and protective effects on the host; however the participating molecules have not been fully defined. Interleukin (IL)-27 is a pleiotropic cytokine exerting both inflammatory and anti-inflammatory effects, but data on IL-27 in malaria patients are scarce.

Methods: Clinical data and blood samples were collected from adults in Mozambique with P.

Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages.

Background And Aims: We have previously found increased levels of the cysteine protease legumain in plasma and plaques from patients with carotid atherosclerosis. This study further investigated legumain during acute cardiovascular events.

Methods: Circulating levels of legumain from patients and legumain released from platelets were assessed by enzyme-linked-immunosorbent assay.

Neutrophil extracellular traps drive inflammatory pathogenesis in malaria.

Neutrophils are essential innate immune cells that extrude chromatin in the form of neutrophil extracellular traps (NETs) when they die. This form of cell death has potent immunostimulatory activity. We show that heme-induced NETs are essential for malaria pathogenesis.

Impaired HDL Function Amplifies Systemic Inflammation in Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency, characterized by inadequate antibody responses and recurrent bacterial infections. Paradoxically, a majority of CVID patients have non-infectious inflammatory and autoimmune complications, associated with systemic immune activation. Our aim was to explore if HDL, known to have anti-inflammatory properties, had impaired function in CVID patients and thereby contributed to their inflammatory phenotype.

Soluble markers of neutrophil, T-cell and monocyte activation are associated with disease severity and parasitemia in falciparum malaria.

Background: The immune response during P. falciparum infection is a two-edged sword, involving dysregulation of the inflammatory responses with several types of immune cells participating. Here we examined T-cell, monocyte/macrophage and neutrophil activation during P.

Circulating delta-like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus-based immunosuppression.

Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx.

Increased Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Ischemic Stroke and Transient Ischemic Attack.

Background: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown to be increased in patients with acute ischemic stroke. Here, we evaluated plasma sLOX-1 levels and vascular carotid plaque LOX-1 (ie, ) gene expression in patients with ischemic stroke and transient ischemic attack (TIA) with particular focus on their relation to time since symptom onset.

Methods And Results: Plasma sLOX-1 (n=232) and carotid plaque gene expression (n=146) were evaluated in patients who were referred to evaluation for carotid endarterectomy, as well as in healthy control plasma (n=81).

Interleukin 27 is increased in carotid atherosclerosis and promotes NLRP3 inflammasome activation.

Aim: Interleukin-27 (IL-27) is involved in different inflammatory diseases; however, its role in atherosclerosis is unclear. In this study we investigated the expression of IL-27 and its receptor in patients with carotid atherosclerosis and if IL-27 could modulate the inflammatory effects of the NLRP3 inflammasome in vitro.

Methods: Plasma IL-27 was measured by enzyme immunoassay in patients with carotid stenosis (n = 140) and in healthy controls (n = 19).

LIGHT/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro.

Aims/hypothesis: Activation of inflammatory pathways is involved in the pathogenesis of type 2 diabetes mellitus. On the basis of its role in vascular inflammation and in metabolic disorders, we hypothesised that the TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) could be involved in the pathogenesis of type 2 diabetes mellitus.

Methods: Plasma levels of LIGHT were measured in two cohorts of type 2 diabetes mellitus patients (191 Italian and 40 Norwegian).

Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation.

Objectives: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD).

Methods: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay.

Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria.

The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria and in human whole-blood specimens stimulated with malaria-relevant agents ex vivo. Complement was significantly activated in the malaria cohort, compared with healthy controls, and was positively correlated with disease severity and with certain cytokines, in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo-stimulated blood specimens, in which complement inhibition significantly reduced IL-8/CXCL8 release.

Cytokine network in adults with falciparum Malaria and HIV-1: increased IL-8 and IP-10 levels are associated with disease severity.

Background: Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection.

Methods: This was a prospective cross-sectional study.

Increased serum and bone matrix levels of the secreted Wnt antagonist DKK-1 in patients with growth hormone deficiency in response to growth hormone treatment.

Context: Growth hormone (GH) substitution of adult-onset growth hormone deficiency (aoGHD) patients partially reverses unfavorable body composition profile. Wnt signaling pathway has being acknowledged as an important modulator of bone mass and of energy metabolism in adipose tissue and in β-cells.

Objective: To assess the role of selected Wnt antagonists in bone and glucose metabolism before and after GH replacement in aoGHD.

Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.

Objectives: Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome.

Cytokine network in scrub typhus: high levels of interleukin-8 are associated with disease severity and mortality.

Background: Scrub typhus, caused by Orientia tsutsugamushi, is endemic in the Asia-Pacific region. Mortality is high if untreated, and even with treatment as high as 10-20%, further knowledge of the immune response during scrub typhus is needed. The current study was aimed at comparing plasma levels of a variety of inflammatory mediators in scrub typhus patients and controls in South India in order to map the broader cytokine profile and their relation to disease severity and clinical outcome.

Increased expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental Rickettsia conorii infection.

Background: Based on their essential role in concerting immunological and inflammatory responses we hypothesized that the homeostatic chemokines CCL19 and CCL21 may play a pathogenic role in rickettsiae infection.

Methods: Serum levels of CCL19 and CCL21 in patients with R. africae and R.