Monocytes In Children Research Articles

Expansion of a Novel Subset of L-Selectin+ Classical Monocytes in Kawasaki Disease.

Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM. Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD. Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD. In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.

Severe neurological impairment and immune function: altered neutrophils, monocytes, T lymphocytes, and inflammasome activation

BackgroundInfections cause significant morbidity and mortality in children with Severe Neurological Impairment (SNI). Alterations in immune cell numbers and function in children with neurodisability have been reported. We aimed to characterise neutrophil, monocyte and lymphocyte proportions and activation, at baseline and in response to stimulation with lipopolysaccharide, in children with SNI compared to healthy controls.MethodsWhole blood samples of children with SNI and controls were incubated in the presence or absence of lipopolysaccharide (10 ng/ml). Monocyte and neutrophil function (Cluster of Differentiation (CD)11b, (TLR)-4 and CD66b expression) and lymphocytes were assessed by flow cytometry. Expression of genes involved in the inflammasome (NLR Family Pyrin Domain Containing(NLRP)-3, Apoptosis-Associated Speck-like protein (ASC) and Interleukin(IL)1β) were assessed by PCR.ResultsMonocytes and CD8+ T cells were lower in children with SNI (n = 14). CD66b, was hyporesponsive and monocyte TLR4 was hyperresponsive to lipopolysaccharide in children with SNI compared to controls (n = 14). NLRP3 expression was higher at baseline and IL1β expression was not upregulated in response to lipopolysaccharide in children with SNI in contrast to controls.ConclusionWe have found significant differences in immune regulation in children with SNI compared to controls which may provide a useful therapeutic target in the future.ImpactChildren with SNI have reduced monocyte and CD8+ T cells.Neutrophils and monocytes in children with SNI show altered markers of activation in response to lipopolysaccharide.Expression of NLRP3 at the RNA level was higher at baseline in children with SNI.This study adds to the existing literature that children with neurological impairment have altered inflammatory and immune cell responses.This may provide a useful therapeutic target to reduce infection-related morbidity and mortality, and tertiary neurological injury in the future.

СВЯЗЬ КОЛИЧЕСТВА CD163+ ПОЛОЖИТЕЛЬНЫХ МОНОЦИТОВ КРОВИ У ДЕТЕЙ С ОЖИРЕНИЕМ

Children obesity is becoming global and causing dysregulation throughout the immune system, affecting the balance and levels of cytokines and adipokines. The purpose of this research was to study the amount of CD14+CD163+ blood monocytes in obese children compared to practically healthy children of normal body weight (BW). Materials and methods used: 70 children aged 9 to 15 y/o were included in a cross-sectional single-center comparative study in parallel groups from Feb. to Nov., 2022. The main group consisted of 60 obese children aged 11.95 (9.45; 14.45) y/o, 43% boys/57% girls. The control group consisted of 10 children without signs of obesity aged 10.4 (9.3; 13.8) y/o, 40% boys/60% girls. The amount of CD14+CD163+ monocytes in peripheral blood was assessed using CytoFLEX platform flow cytometer. All participants have undergone bioimpedance measurement of adipose tissue parameters using InBody 770 body composition analyzer. Results: a statistically significant increase in the amount of CD14+CD163+ blood monocytes was connected with an increase in the obesity class (p=0.010) in children. Thus, in the 2nd and the 3rd obesity classes, an increase in the amount of blood monocytes was noted by 2.8 and 2.6 times, respectively, compared to the children with normal BW (p<0.05). There was also an increase in the amount of CD14+CD163+ monocytes in children with allergic diseases coupled with obesity - by 2.68 times compared to the children without this pathology (p=0.003). Conclusion: the connection between the amount of CD14+CD163+ peripheral blood monocytes, the obesity in children and the development of concomitant pathology was found. Therefore, reprogramming of blood monocytes would probably cause metabolic changes associated with obesity, which in its turn triggers various pathological processes. The results obtained are of a great practical importance for the purposes of treatment correction and undoubtedly require the continuation of the research in the field.

Proinflammatory polarization of monocytes by particulate air pollutants is mediated by induction of trained immunity in pediatric asthma.

The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma, are not well understood. We investigated whether ambient levels of fine PM with aerodynamic diameter ≤2.5 microns (PM2.5 ) are associated with alterations in circulating monocytes in children with or without asthma. Monocyte phenotyping was performed by cytometry time-of-flight (CyTOF). Cytokines were measured using cytometric bead array and Luminex assay. ChIP-Seq was utilized to address histone modifications in monocytes. Increased exposure to ambient PM2.5 was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by the upregulation of proinflammatory mediators, such as TNF, IL-6, and IL-8, upon stimulation with house dust mite or lipopolysaccharide. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution-induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution.

Viral infection‐related gene upregulation in monocytes in children with signs of β‐cell autoimmunity

ObjectiveThe pathogenesis of type 1 diabetes (T1D) is associated with genetic predisposition and immunological changes during presymptomatic disease. Differences in immune cell subset numbers and phenotypes between T1D patients and healthy controls have been described; however, the role and function of these changes in the pathogenesis is still unclear. Here we aimed to analyze the transcriptomic landscapes of peripheral blood mononuclear cells (PBMCs) during presymptomatic disease.MethodsTranscriptomic differences in PBMCs were compared between cases positive for islet autoantibodies and autoantibody negative controls (9 case–control pairs) and further in monocytes and lymphocytes separately in autoantibody positive subjects and control subjects (25 case–control pairs).ResultsNo significant differential expression was found in either data set. However, when gene set enrichment analysis was performed, the gene sets “defence response to virus” (FDR <0.001, ranking 2), “response to virus” (FDR <0.001, ranking 3) and “response to type I interferon” (FDR = 0.002, ranking 12) were enriched in the upregulated genes among PBMCs in cases. Upon further analysis, this was also seen in monocytes in cases (FDR = 0.01, ranking 2; FDR = 0.04, ranking 3 and FDR = 0.02, ranking 1, respectively) but not in lymphocytes.ConclusionGene set enrichment analysis of children with T1D‐associated autoimmunity revealed changes in pathways relevant for virus infection in PBMCs, particularly in monocytes. Virus infections have been repeatedly implicated in the pathogenesis of T1D. These results support the viral hypothesis by suggesting altered immune activation of viral immune pathways in monocytes during diabetes.

Reduced level of CX3CR1 positive T-cells and monocytes in children with, newly diagnosed, Type 1 diabetes

Abstract Background The chemokine CX3CL1 is associated with many autoimmune diseases. Type 1 diabetes (T1D) is an autoimmune disease characterized by an insufficient insulin production due to T-cells mediated destruction of pancreatic beta cells. CX3CL1/CX3CR1 plays an important role in recruitment and extravasation of T-cells and monocytes to the inflammatory site. Aim To investigate the role of CX3CL1 and its receptor CX3CR1 in children with T1D in acute phase (day 0), 10 days and 3 months after treatment compared to healthy subjects (HS). Methods Blood samples from children (range 2–18 years) with new onset type 1 diabetes (day 0 (n=14), day 10 (n=9) and 3 month (n=14)) and 24 age matched HS was collected. The concentrations of CX3CL1 in plasma (T1D day 0, day 10 and HS) was measured by ELISA. Receptor expression of CX3CR1 on monocytes and T-cells was analyzed by flow cytometry. Results The study showed significant higher concentrations of CX3CL1 in serum from T1D day 0 compared to HS (p&amp;lt;0.05) and T1D day 10 (p&amp;lt;0.01). No significant difference was observed between T1D at day 10 and HS. Furthermore, the level of CX3CR1 positive T-cells was significantly lower in T-cells from T1D day 0 compared to HS (p&amp;lt;0.003) and T1D 3 months (p&amp;lt;0.007). In addition, the amount CX3CR1 positive monocytes were significant lower in T1D day 0 compared to HS (p&amp;lt;0.003). Conclusion The low amount of CX3CR1 positive T-cells and monocytes in peripheral circulation in acute phase T1D, despite the high level of s-CX3CL1, indicate that the T-cells and monocytes might have transmigrated to the inflammatory site. This study indicates that CX3CL1/CX3CR1 axis could play a role in the pathogenesis of T1D.

A Carbohydrate Beverage Reduces Monocytes Expressing TLR4 in Children with Overweight or Obesity

Background:Childhood obesity is increasing, with about one-third of children overweight or obese. Obesity is characterized by a state of chronic low-grade inflammation that is related to cardiometabolic comorbidities. Inflammatory monocytes, which are classified into 3 different groups—classical, intermediate, and nonclassical monocytes, with Toll-like receptor 4 (TLR4+) expression indicating a proinflammatory state—underlie several obesity-associated morbidities. Objectives:This study aimed to assess the responses of monocyte populations to beverages of differing macronutrient composition in children with healthy weight (HW) or overweight/obesity (OW/OB). Methods:Ten HW children (5th to 84.9th percentile; mean age 12.29±2.5 y) and 7 children with OW/OB (85th to 99.99th percentile; mean age 11.96±3.8 y) completed the study. Adiposity was determined via DXA. Using a double-blinded, randomized, crossover design, participants consumed either a high-carbohydrate (CHO; 210 kcal; 0g fat/56g carbohydrates/0g protein) or a whole-eggbased high-protein/fat (EGG; 210 kcal; 15g fat/0g carbohydrates/18g protein) beverage. Venous blood was collected at baseline and 2 h postprandially for evaluation of metabolic and inflammatory responses. Repeated measures ANOVA and Pearson correlations were conducted. Results:Consuming the CHO beverage significantly reduced the primary outcome: TLR4+expression on classical monocytes in children with OW/OB only (25.60% decrease from baseline in OW/OB compared with 1.61% increase in HW). Children with OW/OB had significantly less percentages of TLR4+nonclassical monocytes than HW (47.66% lower after CHO). Insulin and glucose (secondary outcomes), were significantly higher after the CHO condition compared with baseline (230.61% and 9.93% increase, respectively). Changes in glucose were significantly and negatively related to changes in monocyte populations in the CHO condition. Conclusions:These data suggest that high-carbohydrate beverages alter monocyte populations in the blood in children with OW/OB, which is related to glucose metabolism. These findings have implications for nutritional recommendations in children with overweight/obesity. National Clinical Trial registry trial number: NCT03597542.

Altered Toll-Like Receptor Signalling in Children with Down Syndrome

Toll-like receptors (TLRs) are the key in initiating innate immune responses. TLR2 is crucial in recognising lipopeptides from gram-positive bacteria and is implicated in chronic inflammation. Children with Down syndrome (DS) are prone to infections from these pathogens and have an increased risk of autoimmunity. Sparstolonin B (SsnB) is a TLR antagonist which attenuates cytokine production and improves outcomes in sepsis. We hypothesised that TLR signalling may be abnormal in children with DS and contribute to their clinical phenotype. We evaluated TLR pathways in 3 ways: determining the expression of TLR2 on the surface of neutrophils and monocytes by flow cytometry, examining the gene expression of key regulatory proteins involved in TLR signal propagation, MyD88, IRAK4, and TRIF, by quantitative PCR, and lastly determining the cytokine production by ELISA following immunomodulation with proinflammatory stimuli (lipopolysaccharide (LPS), Pam3Csk4) and the anti-inflammatory agent SsnB. We report TLR2 expression being significantly increased on neutrophils, total monocytes, and intermediate and nonclassical monocytes in children with DS (n = 20, mean age 8.8 ± SD 5.3 years, female n = 11) compared to controls (n = 15, mean age 6.2 ± 4.2 years, female n = 5). At baseline, the expression of MyD88 was significantly lower, and TRIF significantly raised in children with DS. The TLR antagonist SsnB was effective in reducing TLR2 and CD11b expression and abrogating cytokine production in both cohorts. We conclude that TLR signalling and the TLR2 pathway are dysregulated in DS, and this disparate innate immunity may contribute to chronic inflammation in DS. SsnB attenuates proinflammatory mediators and may be of therapeutic benefit.

Anti leukotrienes Effect on CD64 Expression on Monocytes in Children with Adenoid Hypertrophy

Anti leukotrienes Effect on CD64 Expression on Monocytes in Children with Adenoid Hypertrophy

The significance of M1/M2 macrophage-like monocytes in children with systemic lupus erythematosus

Monocytes/macrophages are important in the development of systemic lupus erythematosus. To research M1 and M2 macrophage-like monocytes in the peripheral blood of children with systemic lupus erythematosus and explore the clinical significance, M1 and M2 macrophage-like monocytes, tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-10, and interleukin-18 are tested in the peripheral blood of children with systemic lupus erythematosus by flow cytometry. A correlation analysis is made between M1 and M2 macrophage-like monocytes and erythrocyte sedimentation rate and C-reactive protein. As we found, the absolute number and percentage of M1 macrophage-like monocytes (CD163–CD14+) in macrophage-like monocytes (CD14+) in peripheral blood of the severe systemic lupus erythematosus group were higher than those of the control group and the mild–moderate systemic lupus erythematosus group ( F = 28.4, 21.7, 122, 81.7; P &lt; 0.05). But there was no obvious difference between these three groups in terms of the absolute number of M2 macrophage-like monocytes (CD163+CD14+). The absolute number and percentage of M1 macrophage-like monocytes in macrophage-like monocytes had positive correlation with C-reactive protein and erythrocyte sedimentation rate ( r = 0.46, 0.44, 0.367, 0.47; P &lt; 0.05); whereas, the absolute number and percentage of M2 macrophage-like monocytes in macrophage-like monocytes had negative correlation with CRP and erythrocyte sedimentation rate ( r = –0.47, –0.45, –0.47, –0.32; P &lt; 0.05). Thus, M1 macrophage-like monocytes have effective impact on inflammation in children with systemic lupus erythematosus. M2 macrophage-like monocytes, to a large extent, have the opposite functions compared to M1 macrophage-like monocytes. In children with systemic lupus erythematosus, macrophages play important role in the development of systemic lupus erythematosus and M1 macrophage-like monocytes have functions in active systemic lupus erythematosus and they can induce the inflammation and have correlation with severity of systemic lupus erythematosus.

OXYGEN-DEPENDENT PHAGOCYTOSIS OF BLOOD MONOCYTES IN CHILDREN WITH HELICOBACTER PYLORI-ASSOCIATED GASTRIC AND DUODENAL EROSIONS AND ULCER

The aim of the research is to study oxygen-dependent phagocytosis of blood monocytes in children with gastric and duodenal erosions and ulcers by chemiluminescence analysis. The subjects of the research were blood monocytes, extracted from blood in 44 children with gastric and duodenal erosions and ulcers in the ages from 11 to 18 years. Microscopic tests for the bioptats of gastric mucosa of both standard regions and edges of ulcer defects had resulted in the determination of 2 groups of the patients with gastric and duodenal erosions and ulcers. The 1st group was represented by Helicobacter pylori high dissemination. As for the 2nd group, the patients showed low bacterization. The tests for luminol-dependent hemiluminescence of blood monocytes in patients with H. pylorihigh dissemination of gastric and duodenal mucosa demonstrated the significant increase of the intensity and the growth of areas both under the curve of spontaneous response and under the curve in the zimozan-induced process as compared to the monocyte activity in the group with low dissemination. Following the lucigenin- dependent chemiluminescence reactions in the group with H. pylori high dissemination we had found significant increase of the time of approaching the peak in both spontaneous response and zimozan- induced processes while the activation index was higher in comparison with phagocyte activities of monocytes in the group with low dissemination. Further stage of the research was to identify CagA-positive strains of H. pylori in the children with gastric and duodenal erosions and ulcers. Studying chemiluminescence activity of blood lymphocytes in the patients with anti-CagA antibodies we found the true increase of the time of reaching the peak, the intensity and the area under the curve in spontaneous process in luminol-dependent response and the time of reaching intensity peak and the intensity of spontaneous chemiluminescence reaction, lucigenin being an activator. So we marked the increase of the activity of oxygen-dependent phagocytosis of blood monocytes in children with H. pylori associated with gastric and duodenal erosions and ulcers related to H. pylori increased bacterization. The growth of H. pylori dissemination results in the higher stage of stomach mucosa inflammation. Therefore active phagocytes generate more intensively the formation of active forms of oxygen, free radicals and the products of peroxide oxidation. CagA-positive strains of H. pylori, as a rule, are associated with the higher level of inflammatory activity than CagA-negative ones. As a result of such influence the functional activity of monocytes increases, because they are «professional » phagocytes. The ability to perform phagocytosis is better expressed in them as compared to other leukocytes.

Dysregulated enzymatic antioxidant network in peripheral neutrophils and monocytes in children with autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder where immune cells play an important role. Oxidants and pro-inflammatory cytokines generated by innate immune cells have been implicated in the pathogenesis of ASD. Many previous reports have shown the role of various enzymatic antioxidants in the plasma/red blood cells of ASD subjects, however no study so far has evaluated them in peripheral immune cells of innate origin (neutrophils and monocytes) in ASD patients and typically developing control (TDC) children. With this background, our study explored the expression and activities of major enzymatic antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) in peripheral neutrophils and monocytes of TDC/ASD subjects. Our data show that expression and activity of SOD is increased in ASD subjects as compared to TDC children in neutrophils and monocytes. On the other hand, GPx/GR activity is either reduced/unaltered in neutrophils and monocytes of ASD subjects as compared to TDC children. Increased SOD expression is associated with upregulated expression of nitrotyrosine (a marker of oxidant damage) in both innate immune cells of ASD subjects. Our study suggests that despite adaptive antioxidant response, there is an increased oxidative burden in peripheral neutrophils and monocytes of ASD subjects. This suggests that dysregulated enzymatic antioxidant network in peripheral innate immune cells could play a significant role in the pathogenesis of autism.

Regulatory Profile Changes of Lymphocytes and Peripheral Blood Monocytes in Children with Candidiasis Associated with Chronic Somatic Diseases

In this paper, we report results of the study of immune parameters with the assessment of regulatory and effector subpopulations of lymphocytes and monocytes with candidiasis in children with chronic somatic diseases (secondary pyelonephritis and obstructive diseases of the upper gastrointestinal tract). Candidiasis was diagnosed by the rising level of circulating Candida albicans mannan antigen and culture mycological research. It was found that the persistence of fungi is associated with differentiated regulatory changes in the structure of subpopulations of lymphocytes and monocytes with preferential increase of immunosuppressive cells (CD4+CD25+hi, CD3+CD16/56+, CD3−CD8+, CD3+4−8−) amid reduction of effector subpopulations of lymphocytes and antigen presenting cells associated with Th1 immune response profile.

EXPRESSION FEATURES OF TOLL-LIKE RECEPTOR 2 AND TOLL-LIKE RECEPTOR 4 IN CHILDREN WITH ASTHMA

Currently actively discussed the role of innate immunity receptors, in particular TLRs in the immunopathogenesis of bronchial asthma (BA). The aim of our work was to study the expression of ТLR2 and TLR4 on the nasal mucosal cells and peripheral blood leukocytes of patients with BA of different severity. The study included 40 children with asthma (3-12 years) and 10 healthy children. Methods: real-time PCR, flow cytometry and multiplex immunofluorescence analysis evaluated the levels of pro and anti-inflammatory cytokines (IL-1β, IL-1ra, IL-6, IL-8, IL-10, TNFα) in nasal swabs. The result of the study hyperactivation of the factors of innate immunity at the level of the mucosal of the nasal cavity in patients with asthma, manifested by increased gene expression of TLR2, TLR4, and production of proinflammatory as well as anti-inflammatory cytokines. Correlation between cytokine levels and the severity of asthma. In the peripheral blood identified a significant increase in the expression of TLR2 and TLR4 on circulating CD14 + monocytes in children with BA. Thus, the increase of gene expression of TLRs mucosa of the nasal cavity, increase surface expression of TLR2 and TLR4 on circulating monocytes of patients with bronchial asthma compared to healthy children. The revealed changes indicate the involvement of the system of TLRs in the immunopathogenesis of bronchial asthma. In the future, TLRs can be used as markers to predict the course of ad and possible therapeutic targets.

Magnitude of viremia, antigenemia and infection of circulating monocytes in children with mild and severe dengue

Dengue is a major public health problem in tropical regions around the world. Viral and immune host factors determine the clinical courses of the infection. We analyzed the dynamics of viremia (by real-time polymerase chain reactions), antigenemia (through detection of the viral non-structural protein [NS]-1 by enzyme-linked immunosorbent assays) and the frequency of virus-infected peripheral blood mononuclear cells (PBMCs) (by multiparametric flow cytometry) in children with primary or secondary dengue virus (DENV) infection in mild to severe cases. Additionally, we evaluated the association of these factors with clinical severity and laboratory parameters. The levels of viremia and antigenemia peaked during the early days of illness and these viral parameters were correlated (rho=0.37, P=0.003). Circulating monocytes were the most naturally infected subset within the PBMCs population, with kinetics similar to those of viremia and antigenemia. The levels of viremia and antigenemia were higher in children with primary infections than in those with secondary infections (P≤0.04). Although there were no associations between the three evaluated factors and clinical severity, the levels of plasma NS1 and the frequency of dengue virus-infected monocytes correlated with prolonged coagulation times. In short, the viremia, antigenemia and infected monocytes were detected early and were not related to clinical severity. The magnitude of antigenemia and infected circulating monocytes was associated with coagulation disorders.

CD163 levels, pro- and anti-inflammatory cytokine secretion of monocytes in children with pulmonary tuberculosis.

Childhood tuberculosis (TB) comprises an important part of the world's TB burden. Monocytes set up the early phase of infection because of innate immune responses. Understanding the changes in monocyte subsets during multisystem infectious diseases may be important for the development of novel diagnostic and therapeutic strategies. The aim of this study was to evaluate the monocyte phenotype together with the cytokine secretion profiles of children with pulmonary tuberculosis. Thirteen patients with pulmonary TB were enrolled as study group, and 14 healthy subjects as control group. Surface expressions of CD16, CD14, CD62L, CD163, CCR2, and HLA-DR of monocytes were analyzed by flow cytometry. The presence of IFN-γ, TNF-α, IL-10, IL-12, IL-23, and soluble form of CD163 (sCD163) in the antigen- and LPS-stimulated whole blood culture supernatants were detected using ELISA and Luminex. Higher percentages of CD14++ CD16+ and CD14+ CD16++ monocyte subsets, and CCR2, CD62L and CD163 expression on circulating monocytes in children with pulmonary tuberculosis were obtained. Diminished levels of ESAT-6/CFP-10-induced IL-10 and increased levels of TB-antigen and LPS-stimulated sCD163 were found in childhood with pulmonary TB. High expression of CD14++ CD16+ , CD14+ CD16++ , CD14+ CCR2+ , and CD14+ CD62L+ cells in childhood TB, and monocyte-derived cytokines reflected both pro- and anti-inflammatory profiles. Higher sCD163 and CD14+ CD163+ monocytes might help physicians in the differential diagnosis of pulmonary TB in children. Pediatr Pulmonol. 2017;52:675-683. © 2016 Wiley Periodicals, Inc.

Monocyte activation and cytokine production in Malawian children presenting with P.falciparum malaria.

SummaryMalaria in malaria‐naïve adults is associated with an inflammatory response characterized by expression of specific activation markers on innate immune cells. Here, we investigate activation and adhesion marker expression, and cytokine production in monocytes from children presenting with cerebral malaria (CM, n = 36), severe malarial anaemia (SMA, n = 42) or uncomplicated malaria (UM, n = 66), and healthy aparasitemic children (n = 52) in Blantyre, Malawi. In all malaria groups, but particularly in the two severe malaria groups, monocyte expression of CD11b, CD11c, CD18, HLA‐DR and CD86, and percentages of TNF‐α‐ and IL‐6‐producing monocytes were lower than in healthy controls, while expression of CD11a, TLR2 and TLR4 was lower in children with severe malaria compared with controls. These levels mostly normalized during convalescence, but percentages of cytokine‐producing monocytes remained suppressed in children with SMA. In all malaria groups, especially the SMA group, a greater proportion of monocytes were loaded with haemozoin than among controls. In a P. falciparum hyperendemic area, monocytes in children with acute symptomatic malaria have reduced expression of adhesion molecules and activation markers and reduced inflammatory cytokine production. This immune suppression could be due to accumulation of haemozoin and/or previous exposure to P. falciparum.

Altered Expression of TLR2 and TLR4 on Peripheral CD14+ Blood Monocytes in Children with Urinary Tract Infection.

Urinary tract infection (UTI) is the second most common bacterial infection, after otitis media, in infants and children. The mechanisms of disease susceptibility and the role of immunity in the pathogenesis of UTI in children have been evaluated. In recent years, Toll-Like Receptors (TLRs) have been recognized as specific components of the innate immune system constituting important mediators in host immune recognition. The aim of the present study was to determine ΤLR2 and TLR4 expression during the acute phase of UTI in infants and children by measuring the CD14/TLR2 and CD14/TLR4 expression on monocytes. We also attempted to compare the TLRs expression with the immunological status of the patients to healthy children. The study group consisted of 60 children (36 females and 24 males) and the control group included 60 age-matched pediatric subjects (27 females and 33 males). In our study, no antibody deficiency was found either in the children with UTI or in healthy subjects. There might be a connection between low IgA, IgG, and IgG subclasses serum levels and UTI as there was a statistically significant difference between patients and healthy children. A higher expression of CD14/TLR2 was revealed in patients (90,07%) compared to controls (85,48%) as well as CD14/TLR4 in patients (90,53%) compared to controls (87,25%) (statistically significant difference, p < 0,05). The results of this study could provide new understanding of UTIs' pathogenesis in children.

Tissue factor-positive monocytes in children with sickle cell disease: relation to vaso-occlusive crisis

Background Hemostatic abnormalities are well documented in sickle cell disease (SCD). Nevertheless, whether these perturbations could contribute toward sickle vasculopathy is still not clear. Aim To evaluate tissue factor (TF) expression (CD142) on monocytes in children with SCD and correlate the results with the clinical state and some inflammatory and coagulation activation markers. Patients and methods This study included 24 children with SCD in steady state, 24 in painful crisis, and 20 healthy age-matched and sex-matched children as controls. The relevant data including the pain rate were retrieved from patients' files. For each participant, complete blood count, prothrombin time (PT%), activated partial thromboplastin time (aPTT), fibrinogen, d-dimer, thrombin-antithrombin complex, and quantitative C-reactive protein were assayed. TF expression on monocytes was analyzed by flow cytometry. Results TF-positive monocytes were significantly higher in both patient groups compared with the controls, being higher in patients in painful crisis (2.06 ± 0.64, 8.01 ± 1.53, and 13.5 ± 4.3 for the controls, steady-state group, and the painful crisis group, respectively, P Conclusion Collectively, these results confirm the prognostic significance of evaluation of TF-positive monocytes in SCD children.

Intravenous immunoglobulin does not increase FcγRIIB expression levels on monocytes in children with immune thrombocytopenia

Intravenous immunoglobulin does not increase FcγRIIB expression levels on monocytes in children with immune thrombocytopenia