Number Of Monocytes Research Articles

Immunological Pre-Metastatic Niche in Dogs With Naturally Occurring Osteosarcoma.

Pre-metastatic niche (PMN) formation is essential for metastatic development and drives organotropism. Tumour-derived extracellular vesicles and soluble factors remodel the microenvironment of distant metastatic organs before subsequent metastasis. Dogs with osteosarcoma (OS) have proven to be excellent disease models for their human companions. Here, we show evidence of PMN formation in dogs with OS before metastasis. We necropsied and sampled lung tissues from dogs with naturally occurring treatment-naïve OS (n = 15) and control dogs without cancer (n = 10). We further divided dogs with OS into those having lung metastases (n = 5) and those without (n = 10). We stained formalin-fixed paraffin-embedded tissues using multiplex immunofluorescence to quantify the number of bone marrow-derived cells, monocytes and macrophages in the lung samples from each dog. The numbers of CD204+ macrophages, CD206+ macrophages and monocytes and CD11d+ bone marrow-derived cells (BMDCs) were significantly higher in the pre-metastatic lung of dogs with OS (n = 10) than in control dogs without cancer (n = 10). Furthermore, the total nucleated cell (DAPI+) density was higher before metastasis than in healthy lungs. In dogs with established metastases, the number of CD11d+ BMDCs was significantly lower than in the pre-metastatic lung, suggesting this recruitment is transient. Our study provides evidence of PMN existence in a naturally occurring cancer model similar to those observed in pre-clinical murine models. BMDCs are recruited to the lungs before metastases have developed. Dogs with OS may represent ideal candidates for assessing new PMN-targeting therapies.

Monocyte/macrophage pyroptosis and C5b-9-induced cyst enlargement in Pkd1-/- mice.

The levels of C5b-9, terminal products of complement activation, were significantly elevated in autosomal dominant polycystic kidney disease (ADPKD). However, the precise mechanisms by which C5b-9 facilitates cyst growth remain incompletely elucidated. Three groups of chronic-onset Pkd1-/- mice were established: one group received intravenous injections of 0.5 mg/kg C5b-9, another was administered 1.0 mg/kg monoclonal anti-C9 antibodies, and a control group received 1 mg/kg IgG isotype control (IC). All treatments were administered biweekly for two months (postnatal day [PD] 180-240). Renal macrophages from distinct subsets were sorted using fluorescence-activated cell sorting (FACS). To deplete macrophages, liposome clodronate (LC) was injected intraperitoneally. Sublethal irradiation followed by bone marrow (BM) reconstruction was performed in Pkd1-/- mice to evaluate the role of BM-derived macrophages (BMDMs) in ADPKD progression. (1) In vitro, sublytic C5b-9 did not affect the viability of renal tubular epithelial cells (RTECs), but significantly induced M1-like polarization and pyroptosis of BMDMs. (2) In vivo, C5b-9 notably triggered pyroptosis of Ly6C+ monocytes and a reduction in circulating monocyte numbers as cysts enlarged. (3) Residual Ly6C+ monocytes infiltrated renal tissues and differentiated into Ly6C+ macrophages, which exhibited a greater susceptibility to pyroptosis compared to Ly6C- macrophages. (4) Although limited evidence has recently suggested that Ly6C- monocytes may also be affected by C5b-9, upregulation of CCR2 in Ly6C- macrophages was observed in C5b-9-treated Pkd1-/- mice, implying that Ly6C- monocytes could represent a significant source of M2 macrophages. C5b-9 infusion promoted RTEC proliferation by inducing pyroptosis of Ly6C+ monocytes/macrophages, contributing to progressive cyst enlargement in chronic-onset PKD mice.

Immune cell changes in Helicobacter pylori infection-induced glandular epithelial cell damage of the gastric mucosa

Objective The purpose of this study was to investigate the relationship between Helicobacter pylori (H. pylori) infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and the histopathological characteristics of these changes. Methods We performed a detailed histomorphometry and immunohistochemical analysis of a total of 1635 H. pylori-infected gastric mucosal specimens. Results Stage-wise features were as follows: Early stage of infection: H. pylori was colonized in the mucous layer, and very few neutrophils were visible in the layer. Gastric surface epithelial cell infection stage: H. pylori specifically and selectively adhered to the cytoplasm of the surface mucous cells, with the presence of a small number of neutrophils, eosinophils, and lymphocytes infiltration, which is termed early immune response. Compensatory mucous neck cell hyperplasia stage: proliferation of stem cells in the deep gastric pit and infiltration of a large number of lymphocytes in the superficial layer of lamina propria were observed, which is termed immune cell mobilization counterinsurgency. Lamina propria lesion stage: excessive upward migration of the proliferative area. Infiltration of a large number of lymphocytes, plasma cells, monocytes, macrophages, and other immune cells was observed in the whole layer of the gastric mucosa, which is termed automatic replication of immune cells. Abnormal proliferative transformation stage: presence of intranuclear milky globular body cells or signet-ring cell-like heterotypic cells at the junction of the gastric pit and the gastric gland, with proliferation of large numbers of immune cells and vacuolar degeneration of immune cells, which is termed the proliferation and degeneration of immune cells. Intraepithelial neoplasia stage: clonal hyperplasia of epithelial cells and immunosuppression. Conclusion For controlling the occurrence and development of gastric cancer and effective immune intervention, it is essential to grasp the relationship between H. pylori infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and its histopathological characteristics.

Identification of Some Fungi Causing Skin Infection and its Relationship with Some Blood Test of Tinea Patients in Tikrit City

Dermatophytes infection is a common problem worldwide and frequent in Iraq. Several reports and articles were published on prevalence, distribution, causes and treatment of dermatophytosis. The current study included the collection of 100 clinical samples (70 skin peels, 20 hair samples and 10 nail samples), as well as 50 blood samples from patients with dermatophytes and skin consultants in Tikrit City and 20 healthy blood samples for the period from November 2023 to March 2024. The results showed that the most common dermatophytes isolated was Microsporum canis and T.rubrum 10 (20 %) isolates from 50 total , followed by M.gypseum, 6(12%) and 5(10%) T.mentagrophytes and T.verrucosum and 4(8 %) isolates E. floccosum and T.erinacei and finally appeared 3(6 %) isolate T.schoenleinii and T.concentricum. The results of the statistical analysis showed non significant difference P <0.05 in the total number of white blood cells and monocyte (5.15 ± 2.636, 0.89±0.51) in patients with dermatophytes compared with the group Control mean± SD (5.73±1.821, ± 0.69 ± 1.591) respectively. Lymphocytes significant decreased (1.82 ± 1.301) in patients with dermatophytes compared to control group (4.60 ± 1.35) P≤0.01. Furthermore granlocytes increased (2.30±1.591) in patients with dermatophytes compared to control group (0.33± 0.403) P<0.01. The study concluded that perhaps the reduction of some of the body's WBCs parameters has an important role in the incidence of fungal infection in people infected with them when compared to healthy people.

Features of changes in nonspecific factors of immunological reactivity in obesity

Introduction. The study of pathogenetic factors of obesity is an urgent task of modern medicine. The formation of obesity is characterized by changes in the activity of individual mechanisms of innate immunity. At the same time, the values of laboratory indicators that characterize them are often within the current boundaries of the reference values of laboratory indicators of the immunity of a healthy person. This complicates the pathogenetic assessment of the mechanisms of nonspecific immunological reactivity in obesity and determines the need for further study of the characteristics of nonspecific immune defense factors in this pathology.Aim. To identify the features of changes in cellular and humoral factors of nonspecific immunological reactivity in obesity.Materials and methods. A single-center cross-sectional, one-time controlled study was conducted with the participation of 118 people, of which 87 people were obese patients (BMI 37.2 [34.1; 42.05] kg/m2), 31 people had normal body weight (BMI 21.9 [ 20.2; 23.5] kg/m2) and were included in the control group. All patients underwent a study of lipid profile (total cholesterol, high-density lipoproteins, low-density lipoproteins, very low-density lipoproteins, triglycerides), carbohydrate metabolism (glucose, insulin, glycated hemoglobin), C-reactive protein, indicators of cellular and humoral factors of nonspecific immunity (leukogram, cytokine profile, C3-C4 complement components).Results. An increase in the total number of leukocytes was revealed, due to neutrophil granulocytes against the background of the development of a disproportion between the percentage and absolute value of the number of lymphocytes and monocytes, the concentration of C3 and C4 complement components, C-reactive protein, as well as an increase in the level of IL-6, which confirms the presence of low-grade chronic inflammation in obese patients. Statistically significant correlations of immunological parameters with anthropometric data, indicators of carbohydrate and lipid metabolism were revealed.Conclusion. The results of the study indicate that obesity causes activation of certain cellular and humoral mechanisms of nonspecific immune defense involved in the formation of the inflammatory process. Confirmation of the presence of a latent inflammatory process in obesity is an increase in the level of leukocytes and their individual cellular forms, C-reactive protein, C3 and C4 complement components, IL-6. A feature of the changes is the presence of fluctuations in the values of the studied indicators within the current boundaries of the reference values of laboratory indicators, which makes it difficult to timely diagnose chronic inflammation in obesity

Оцінка інформативності клініко-інструментальних та лабораторних показників у виявленні активності патогенетичних факторів, асоційованих зі змінами перебігу інфаркту міокарда в період воєнного стану

The aim – to establish markers of clinical and functional state development in patients with acute myocardial infarction inherent in wartime.Materials and methods. A cohort of 133 STEMI patients was examined (77.4 % men, 61.7±0.9 years). Part of the patients (group 1) was hospitalized from February to May 2019 (n=87), while the other part of them (group 2) was hospitalized in the period from February 24, 2022 to May 2023 (n=46) within the first 24 hours from the development of symptoms (average time of admission 5.2±0.4 hours). In order to eliminate discrepancies in indicators, which with a low probability are related to the action of wartime factors, comparable samples were made from groups 1 and 2 (52 patients and 17 patients, respectively). Comparison of groups was carried out based on clinical and anamnestic and laboratory parameters of the first day.Results and discussion. At the admission to the hospital, markers of a specific clinical and functional state in patients with STEMI due to the influence of wartime factors are: level of leukocytes > 13.0 · 109/L, monocytes > 0.5 · 109/L, lymphocytes > 1.2 . 109/L, triglycerides > 1.63 mmol/L, heart rate > 76 beats/min, as well as criteria made up of these indicators (in particular, products of the level of monocytes or lymphocytes, the level of triglycerides and heart rate, as well as the 7-component scale, which takes into account heart rate, ESR, glucose and triglyceride levels, as well as the number of monocytes, lymphocytes and platelets). Moreover, the increase in the number of monocytes is not associated with hospital complications in these patients. Instead, the level of triglycerides, the number of lymphocytes and platelets are directly related both to the influence of wartime factors and to the complicated hospital course of STEMI.Conclusions. The influence of wartime factors in patients with STEMI is combined with the response to myocardial damage. It leads to an increase in the risk of a complicated course of the hospital stage, as well as to specific clinical and laboratory changes. These changes make it possible to recognize the impact of wartime factors and patients at high risk of hospital course of myocardial infarction.

Laboratory possibilities of prognosis of local complications in hip replacement

BACKGROUND: Endoprosthetics of large joints is a frequently performed operation in traumatology practice. The progression of local infectious sequela among postoperative patients is of major socio-economic importance since more than 30% of cases of inflammatory postoperative reactions are complicated by sepsis. In recent years, new criteria have been sought to assess the risks of infection in the field of surgical intervention, and prognostic scales have also been developed. AIM: The aim of the study was to evaluate the prognostic value of coagulological, biochemical and hematological indicators of the risk of hemorrhagic complications in patients after hip replacement. MATERIALS AND METHODS: The study included 85 patients who were in the clinic of Traumatology and Orthopedics of the I.I. Mechnikov for planned hip replacement. The average age of the patients was 64 ± 10 years. There were 46 women (54%), 39 men (46%). All patients underwent clinical and laboratory examination before surgery, the day after surgery and before discharge. All patients received rivaroxaban (10 mg 1 time/day) after surgery for the prevention of venous thromboembolic complications (46 patients) or apixaban (2.5 mg 2 times/day) (39 patients) during the entire period of stay in the clinic. Retrospectively, depending on the occurrence of complications, the patients were divided into 2 groups: group 1 — 78 patients (42 women and 36 men), whose postoperative period passed without complications, and group 2 — 7 patients (4 women and 3 men), who had hemorrhagic cases. Screening coagulogram (International Normalized Ratio, Activated partial thromboplastin time, fibrinogen) was performed on the STA Compact analyzer (Stago, France), biochemical parameters (alanine aminotransferase, aspartate aminotransferase, creatinine, total calcium, ionized calcium, serum iron, C-reactive protein) were determined on the COBAS Integra 400plus analyzer, hematological parameters on the DxH800 analyzer (Beckman Coulter, USA). RESULTS: A retrospective analysis revealed that a decrease in serum iron in male patients before surgery is a marker of the prognosis of hemorrhagic complications. Prognostic significant laboratory indicators of the development of hemorrhagic complications in patients in the early period after hip replacement include an increase in fibrinogen and C-reactive protein; a decrease in serum iron. During the recovery period, the concentration of C-reactive protein and the relative number of monocytes are the most significant for assessing the risk of complications. CONCLUSIONS: Among the laboratory indicators in the structure of the weight coefficients of the prognosis of complications in patients undergoing hip replacement, it is necessary to evaluate the concentration of serum iron before surgery, especially in men, in the early postoperative period — C-reactive protein, fibrinogen and serum iron and at discharge — C-reactive protein and the number of monocytes as additional criteria for the risk of complications.

Enriched Diet With Orange Essential Oil Citrus sinensis for Tambaqui Colossoma macropomum Promotes Growth Performance and Resistance Against Aeromonas hydrophila.

The objective of this study was to evaluate the effect of dietary supplementation with Citrus sinensis (L.) Osbeck essential oil on the growth, immune system, and resistance to Aeromonas hydrophila infection in Colossoma macropomum fingerlings. The experiment was conducted with five treatments (control diet, Tween80 diet, and diets supplemented with 200, 400, and 800 mg L-1 of C. sinensis essential oil) with four replicates. At the end of the experimental period, growth parameters were measured, and blood samples were collected for thrombogram, leukogram, and phagocytic activity analysis. A bacterial challenge with A. hydrophila was conducted for 96 h. C. macropomum fingerlings that were fed with 400 and 800 mg L-1 of C. sinensis essential oil had the highest growth parameters, with final weights of 533.18 ± 2.03 mg and 531.91 ± 2.67 mg, respectively, and an increase in the number of thrombocytes, lymphocytes, monocytes, and neutrophils, as well as higher phagocytosis rates compared to the control group. Regarding the challenge, fish in the 400 and 800 mg L-1 treatments also exhibited the lowest cumulative mortality rate (26.66% ± 3.33%). Therefore, supplementation with C. sinensis essential oil promotes growth, improves health, and enhances resistance to A. hydrophila in C. macropomum fingerlings.

Protective role of Metrnl on macrophage recruitment during the acute inflammatory phase in a mouse model of myocardial infarction

Abstract Introduction Meteorin-like protein (Metrnl) is a cytokine involved in the attenuation of inflammation. Previously, a cardioprotective role of Metrnl against cardiac hypertrophy and ischemia/reperfusion has been described. After myocardial infarction (MI), macrophages recruited from the spleen, and their capacity to shift from inflammatory (M1) to reparative (M2) phases determines the fate of cardiac repair. Purpose The aim of this study was to analyse the function of Metrnl in a mouse model of permanent MI during the acute inflammatory phase. Methods Wild-type (WT), Metrnl Knock-out (Metrnl-/-) and Metrnl-reconstituted Metrnl-/- mice (AAV9-Metrnl, with myocardial-specific tropism) were subjected to MI by coronary artery ligation. After 4 days, cardiac function was assessed using echocardiography at baseline and 4 days post-MI. Monocyte populations were analysed in spleen and blood by flow cytometry, and macrophages infiltrating the infarcted myocardium by gene expression analyses. Results Echocardiographic analysis demonstrated that Metrnl deficiency led to cardiac dysfunction (FAC p=0.02) accompanied by myocardial dilation 4 days post-MI (EDV p=0.02; ESV p=0.01). On the contrary, the overexpression of Metrnl in the myocardium of AVV9-Metrnl mice restored cardiac function compared to Metrnl-/- group (FAC p=0.01, EDV p=0.04, ESV p=0.09). Furthermore, we observed a reduction in splenic monocytes (CD11b+F4/80+) in Metrnl-/- mice compared to the WT group at 4 days post-MI (p=0.06). In particular, a significant decrease in pro-inflammatory Ly6CHigh and CD86+ monocytes was noted in the spleens of Metrnl-/- mice compared to the WT group (p=0.03; p=0.04 respectively), suggesting their mobilization out of the spleen, but not in the AVV9-Metrnl group. Although the total number of Ly6CHigh and Ly6CLow monocytes in the bloodstream was similar in all groups, there was a trend to different expression in the CCR2 and CCR5 chemokine receptors (p=0.07; p=0.06 respectively). At the same time, M1 macrophage recruitment chemokines (CCL2) and inflammatory markers (TNFα) were significantly induced in the ischemic area of the infarcted myocardium compared to the remote zone in the WT and Metrnl-/- groups (CCL2 p=0.03; p=0.01 respectively; TNFα p=0.008;p=0.04 respectively). In contrast, TNFα and CCL2 genes were not induced in the ischemic area of AVV9-Metrnl mice. Regarding M2 macrophages, the Arg1 marker was significantly reduced in the ischemic zone of Metrnl-/- mice compared to the WT group (p= 0.01), while in the AVV9-Metrnl group was recovered (p= 0.04). Conclusions Our results demonstrate that the absence of Metrnl promotes the recruitment of inflammatory macrophages to the ischemic myocardium and is associated to cardiac dysfunction.

Role of Galectin-3 in resident macrophages and effects on atherosclerosis

Abstract Background Arterial macrophages play an important role in atherosclerosis, exhibiting heterogeneity in their origins as either resident or inflammatory monocyte-derived macrophages. Resident macrophages originate predominantly from the yolk sac, and they are endowed with homeostatic functions and can have anti-inflammatory properties under inflammation [1]. Resident macrophages pre-existing within the tissue differentiate into foamy macrophages before monocytes appear in early atherosclerotic lesions [2]. Galectin-3 (Gal-3) encoded by the gene Lgals3, is a crucial effector molecule that is prominently expressed by macrophages [3]. Studies have provided conflicting evidence regarding the role of Gal-3 in atherosclerosis by affecting macrophage functions and monocyte recruitment [4,5]. Purpose This study aims to investigate the role of Gal-3 in arterial resident macrophages for atherosclerosis and reveal the underlying mechanisms. Methods General Lgals3 knockout (Lgals3-/-) and resident macrophage specific knockout (Lgals3-/-Rank-Cretg) mice on the Apoe-deficient background were generated and atherosclerotic lesion development (8 weeks of western diet) was compared. Results Our study revealed that Lgals3-/- mice exhibited increased numbers of monocytes and neutrophils in the blood, which was associated with the development of larger atherosclerotic plaques. Plasma Gal-3 concentration from Lgals3-/-Rank-Cretg mice was decreased by 60%, indicating that the majority of circulating Gal-3 is derived from resident macrophages. Surprisingly, Lgals3-/-Rank-Cretg mice did not show the observed increase in blood monocytes and neutrophils, suggesting that this effect was independent of circulating Gal-3. Consistent with a causal role of monocytosis and leukocytosis in atherogenesis, plaque formation in Lgals3-/-Rank-Cretg was not significantly affected. Additionally, Gal-3 deficiency promoted M1 polarization and reduced efferocytosis, phagocytosis and chemokine receptor expression in BMDMs, and the addition of exogenous Gal-3 restored the effect on phagocytosis and blocked CXCL12 and CCL5-induced leukocyte migration. Conclusion This study reveals a prominent protective role of Gal-3, primarily through inflammatory macrophages rather than resident macrophages for the development of atherosclerotic lesions. This protective effect is attributed to its homeostatic effects on monocyte and neutrophil numbers, as well as its influence on macrophage functions.

The paradigm of possibilities leading to the formation of autoimmune and infectious phenotypes of common variable immune deficiency

The term variable in the definition of CVID is associated with the heterogeneity of the genetic nature and clinical manifestation of this variant of PI. Deciphering of the mechanisms or identifying biomarkers of clinical heterogeneity may be important in the timely diagnosis and prognosis of the course of CVID. The purpose of the study was to identify distinctive features in the parameters of the innate and adaptive immune response of the patients with infectious and autoimmune manifestations of CVID in remission and clinical manifestation. Fifteen patients, 11 women and 4 men with an average age 39.7±11.7 years were examined, and they were divided into two subgroups depending on clinical verification: infectious phenotype (10 people) and autoimmune phenotype (5 people). In the absence of clinical signs of activation of autoimmune pathology or exacerbation of chronic infectious processes, peripheral blood monocytes became the application point of distinctive values. An increase in the number of TLR9-expressing monocytes has been shown in patients with autoimmune clinical verification of CVID. The differences in the parameters of the immune status of patients conducted during the period of clinical manifestation consisted of a decrease in the relative content and absolute number of T regulatory lymphocytes, and an increase in the number of monocytes containing TLR9, TLR2 and HLA-DR in patients with an autoimmune phenotype relative to the subgroup with infectious manifestation. The data obtained reflect the involvement of the immunoregulatory potential of the immune system in the clinical manifestation of primary immunodeficiency, even under the conditions of pathogenetic substitution therapy. The evidence of the stated position is a decrease in immunosuppression in autoimmune manifestation due to a decrease in the number of peripheral T-regulatory cells and a smaller proportion of monocyte cells belonging to the M2 suppressive category. Attention is also drawn to the increased potential of primary response to patterns of various nature in autoimmune manifestation due to an increase in the number of monocytes expressing Toll-like receptors of various specificity. The presented results can be proposed as a diagnostic and prognostic indicator of the difference in clinical phenotypes of CVID.

Влияние избыточной массы тела и ожирения на спирометрические, гематологические показатели, уровень общего иммуноглобулина Е и интерлейкина-6 в сыворотке крови у детей и подростков с бронхиальной астмой

There is undoubtedly insufficient number of studies dedicated to the interleukin-6 (IL-6) in blood serum of children and adolescents with bronchial asthma (BA) and those are contradictory. Connection between the IL-6 serum level and systemic markers of type 2 inflammation in BA in children and adolescents depending on the nutritional status remains a subject to discussion as well. The purpose of this research was to study the effect of excess body weight (BW) and obesity on spirometric, hematological parameters, total immunoglobulin E (IgE), IL-6 levels in blood serum of children and adolescents with BA. Materials and methods used: a single-center observational cross-sectional pilot study of 76 adolescents aged 6 to 17 y/o (75% (57) boys) with BA was conducted. All were measured for anthropometric and spirometric parameters, body composition, hematological parameters, total IgE and IL-6 levels in blood serum. Dysanapsis was diagnosed when three conditions were simultaneously met: 1. high or high-to-normal zFVC (above 0.674), 2. normal zFEV1 (above -1.645), and 3. low FEV1/FVC index (below 80%). Results: the number of monocytes (109/l) in peripheral blood and the serum IL-6 level (pg/ml) were statistically significantly higher in the group of patients with overweight and obesity compared to patients with underweight/normal BW (0.55 [0.49; 0.77] v 0.51 [0.42; 0.58], p=0.043 and 1.99 [1.20; 5.78] v 1.28 [0.31; 2.43], p=0.002, respectively). In patients with excess BW and obesity, an inverse statistically significant relationship was found between the serum IL-6 level, zFEV1/FVC and the dysanapsis ratio (R=-0.53, p=0.009, R=-0.61, p=0.002, respectively). Conclusion: formation of an obstructive pattern in children and adolescents with BA with excess BW and obesity may be associated with non-T2-dependent inflammatory mechanisms.

Patients with coronary atherosclerosis had an altered ratio of monocyte subpopulations in the blood, which was associated with an inflammatory cell response

Coronary artery disease (CAD) is one of the leading causes of death in developed countries. Experimental data confirm the role of monocytes in the development of CAD. Three main subpopulations of circulating blood monocytes are known: classical CD14++CD16- (~80%), intermediate CD14+CD16+ (~5%) and non-classical CD14+CD16++(~15%). It is believed that each of the subpopulations of monocytes performs different functions. There are studies that demonstrate that classical monocytes respond more to the bacterial presence, whereas non-classical ones respond to the viral one. However, the functions of monocyte subpopulations have not been fully studied. Previously, we demonstrated that circulating monocytes of the blood of patients with atherosclerosis had increased proinflammatory activity. We decided to find out how the ratio of monocyte subpopulations in the blood is related to the inflammatory response of cells in atherosclerosis. The aim of our work was to investigate the relationship of the inflammatory response of primary monocytes with the distribution of monocyte subpopulations relative to the total pool of monocytes in healthy and sick CAD. The study included 20 men aged 46 to 70 years, 10 of them without CAD and 10 patients with CAD. A coronary angiography was performed, according to the results of which the patients were divided into patients with coronary atherosclerosis with detected stenosis in 2 or more arteries (CAD) and healthy ones without stenosis in the arteries. Next, blood was taken to study circulating monocytes. Monocyte subpopulations were detected by flow cytometry from the leukocyte fraction using antibodies against CD14- FITC and CD16-PB450-A. Immediately after isolation, monocytes were stimulated with LPS with a final concentration of 1 ug/mL, and a supernatant was selected 24 hours later for further enzyme immunoassay. The inflammatory response was assessed by the secretion of cytokines TNFα, IL-1β, IL-6, IL-8, IL-10, and CCL2 using ELISA. The monocytes of CAD patients had an altered inflammatory response in response to LPS stimulation compared to patients without CAD. This was manifested in increased secretion of IL-1β and TNF, and decreased secretion of CCL2 and IL-6. An increase in the number of intermediate and non-classical monocytes in patients with CAD was associated with changes in the inflammatory response of cells to the secretion of cytokines IL-1β and CCL2. It can be assumed that pathological changes in the representation of monocyte subpopulations in the bloodstream may be one of the causes of chronic inflammation in the walls of the arteries, contributing to the progression of atherosclerotic lesions.

Diethylhexyl phthalate induces immune dysregulation and is an environmental immune disruptor

Diethylhexyl phthalate (DEHP) is the most abundant phthalate compound in the environment, and has been linked with multiple human diseases. The immune system is closely associated with the occurrence and progression of various diseases. However, minimal research has addressed the impact of DEHP on the immune system. In this study, single-cell RNA sequencing was performed using spleen tissue of mice to comprehensively determine alterations of the immune system in response to DEHP. The results showed that DEHP exposure reduced the absolute number of peripheral white blood cells (WBCs), including lymphocytes, monocytes, eosinophils, basophils, and neutrophils in mice. In addition, scRNA-seq analyses showed that inflammatory signaling and the expression of heat shock proteins (HSPs) were reduced in all peripheral immune cell populations. Furthermore, we established a mice cecal ligation and puncture (CLP) model, and showed that DEHP exacerbated sepsis-induced immunosuppression and organ damage. These results suggest that DEHP is an environmental immune disruptor that undermines the immune system, exacerbating acute infections and organ damage. Our findings offer a novel perspective on the hazards of DEHP to human health.

Glucose metabolism controls monocyte homeostasis and migration but has no impact on atherosclerosis development in mice

Monocytes directly contribute to atherosclerosis development by their recruitment to plaques in which they differentiate into macrophages. In the present study, we ask how modulating monocyte glucose metabolism could affect their homeostasis and their impact on atherosclerosis. Here we investigate how circulating metabolites control monocyte behavior in blood, bone marrow and peripheral tissues of mice. We find that serum glucose concentrations correlate with monocyte numbers. In diet-restricted mice, monocytes fail to metabolically reprogram from glycolysis to fatty acid oxidation, leading to reduced monocyte numbers in the blood. Mechanistically, Glut1-dependent glucose metabolism helps maintain CD115 membrane expression on monocytes and their progenitors, and regulates monocyte migratory capacity by modulating CCR2 expression. Results from genetic models and pharmacological inhibitors further depict the relative contribution of different metabolic pathways to the regulation of CD115 and CCR2 expression. Meanwhile, Glut1 inhibition does not impact atherosclerotic plaque development in mouse models despite dramatically reducing blood monocyte numbers, potentially due to the remaining monocytes having increased migratory capacity. Together, these data emphasize the role of glucose uptake and intracellular glucose metabolism in controlling monocyte homeostasis and functions.

Immunological resilience of a temperate catshark to a simulated marine heat wave.

Marine heatwaves (MHW) have recently been proposed as more relevant in driving population changes than the continuous increase in average temperatures associated with climate change. The causal processes underpinning MHW effects in sharks are unclear but may be linked to changes in fitness caused by physiological trade-offs that influence the immune response. Considering the scarcity of data about the immune response of sharks under anomalous warming events, the present study analyzed several fitness indices and characterized the immune response (in the blood, epigonal organ, liver, spleen, and intestine) of temperate adult small-spotted catsharks (Scyliorhinus canicula) after a 30-day exposure to a Category II MHW. The results indicated that adult small-spotted catsharks have developed coping strategies for the MHW. Specifically, among the 35 parameters investigated, only the gonad-to-body ratio (GBR) and plasma glucose showed significant increases. In contrast, igm and tumor necrosis factor receptor (tnfr) gene expression in blood cells, tnfr in the epigonal organ, and the number of monocytes significantly decreased. Although a decline in immune function in small-spotted catsharks was revealed following the MHW exposure, energy mobilization restored homeostasis and indicated a shift in energy allocation towards reproduction. Group resilience may be due to the variable tolerance of individuals, the phenotypic plasticity of cellular immunity, thermal imprinting, and/or metabolic capacity of the individuals.

Association of circulating monocyte number and monocyte–lymphocyte ratio with cardiovascular disease in patients with bipolar disorder

BackgroundCardiovascular disease (CVD) is the leading cause of excessive and premature mortality in patients with bipolar disorder (BD). Despite immune cells participating considerably in the pathogenesis of CVD, limited data are available regarding leukocyte phenotypes in patients with BD and CVD. This study aimed to evaluate associations between circulating leukocyte subset and CVD among patients with BD.MethodsA total of 109 patients with BD-I and cardiologist-confirmed CVD diagnosis (i.e., case) were matched with 109 BD-I patients without CVD (i.e., control) according to the age (± 2 years), sex, and date of most recent psychiatric admission because of acute mood episode (± 2 years). Leukocyte subset data were retrieved from complete blood count tests performed on the next morning after the most recent acute psychiatric admission.ResultsDuring the most recent acute psychiatric hospitalization, circulating monocyte counts in the case group were significantly higher than those in the age- and sex-matched controls (p = 0.020). In addition, monocyte–lymphocyte ratios (MLRs) in the case group were significantly higher than those in the control group (p = 0.032). Multiple logistic regression showed that together with serum levels of uric acid and manic symptoms, circulating monocyte counts (95% CI, OR: 1.01–1.05) and MLRs (95% CI, OR: 1.01–1.09) were significantly associated with CVD in patients with BD, respectively.ConclusionsMonocyte activation in an acute manic episode may play a critical role in the pathogenesis of CVD among patients with BD. Future research is required to investigate markers of monocyte activation and indices of cardiovascular structure and function across the different mood states of BD.

Increased CRHR1 expression on monocytes from patients with AA enables a pro-inflammatory response to corticotrophin-releasing hormone.

Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (n = 54) and controls (n = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, p = 0.002, chi-squared test). AA incidence was correlated to elevated CD14+ monocyte numbers (R = 0.092, p = 0.036) and markedly independently correlated with increased CRHR1 expression (R = 0.215, p = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration >1 year; p = 0.003, chi-squared test), and large lesion area (AA area >25%; p = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16+ CD3- NK cell numbers in AA patients' PBMCs (p = 0.010; 0.025, respectively). Invitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.

Evaluation of plant commercial feed additives for equine cyathostomin control

The increasing emergence of anthelmintic-resistant parasitic isolates prompts us to reassess the management of intestinal strongylosis in horses. Additionally, societal demand is shifting toward reducing the use of chemical treatments, aligning with environmentally-friendly practices and the exploration of natural alternatives. In this context, we provide an initial view of the antiparasitic activity and the effect on immune circulating blood cells of three commercialized plant-based feed additives in ponies. Three treatments, based either on mugwort (Artemisia vulgaris), echinacea (Echinacea purpurea) or curcumin (Curcuma longa) were administrated to 18 (six per treatment) Welsh female ponies naturally infected with cyathostomins to mimic their practical use in farming conditions. Another group of six untreated ponies was used as a control. Fecal egg count (FEC), the larval development percentage and the number of red blood cells, lymphocytes, monocytes, neutrophils, eosinophils and basophils were measured the first and the last day of each treatment, and compared with those characterizing the control group. None of the three treatments showed a significant effect on the studied parameters. Moreover, the efficacy of treatments, measured from the FEC reduction compared to the control group, was weak (≤ 38.6 %). Therefore, these results do not support the practical use of these additives in equine farming, even if the determination of Cohen's d values associated with the three treatments revealed some incidences on FEC and blood immune cell counts, as well as on larval development for mugwort.

Age-associated changes in innate and adaptive immunity: role of the gut microbiota.

Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to its profound implications for the health and well-being of the aging population. As people age, a multitude of alterations occur within the immune system, affecting both innate and adaptive immunity. In the realm of innate immunity, aging brings about changes in the number and function of various immune cells, including neutrophils, monocytes, and macrophages. Additionally, certain immune pathways, like the cGAS-STING, become activated. These alterations can potentially result in telomere damage, the disruption of cytokine signaling, and impaired recognition of pathogens. The adaptive immune system, too, undergoes a myriad of changes as age advances. These include shifts in the number, frequency, subtype, and function of T cells and B cells. Furthermore, the human gut microbiota undergoes dynamic changes as a part of the aging process. Notably, the interplay between immune changes and gut microbiota highlights the gut's role in modulating immune responses and maintaining immune homeostasis. The gut microbiota of centenarians exhibits characteristics akin to those found in young individuals, setting it apart from the microbiota observed in typical elderly individuals. This review delves into the current understanding of how aging impacts the immune system and suggests potential strategies for reversing aging through interventions in immune factors.