scholarly journals CD23 Mediates Innate Immunity Against Aspergillus Fumigatus Infection in Human Alveolar Macrophages Through Activation by PU.1

2021 ◽  
Author(s):  
Min Wang ◽  
Ming Zhang ◽  
Jiayong Qiu ◽  
Chenyang Liu ◽  
Yao Lou ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Aspergillus Fumigatus ◽  
Alveolar Macrophages ◽  
Inflammatory Markers ◽  
Inflammatory Marker ◽  
Mouse Lung ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lectin Receptors ◽  
Human Alveolar Macrophages ◽  
Cd23 Expression

Abstract Aspergillosis is a common cause of morbidity and mortality in immunocompromised populations. CD23 is a novel C-type lectin receptors (CLR) recognizing α-mannan and β-glucan in the cell wall of Aspergillus fumigatus (AF) that exerts a host innate immune response. However, the molecular mechanism underlying CD23 mediating immunity against AF infection in human alveolar macrophages is still unclear. In this study, we detected the expression of CD23 and PU.1 and the inflammatory markers IL-1β, IL-6, TNF-α and IL-10 by qRT–PCR, Western blotting and enzyme linked immunosorbent assay (ELISA) analysis in human alveolar macrophages (AMs) with AF infection. Phagocytosis of macrophages with altered CD23 expression and histological changes in lung tissues transfected with CD23-expressing adenoviruses in AF infection were investigated. Dual luciferase, chromatin immunoprecipitation assay (ChIP) and electrophoretic mobility shift assay (EMSA) was performed to detect the interaction of PU.1 and CD23. The results showed that the expression of CD23, PU.1 and these inflammatory markers increased significantly with the time of AF infection. Increasing CD23 expression strengthened the phagocytosis of AMs, and exogenous CD23 attenuated pathological defects in immunodeficient mouse lung tissues with AF infection. Moreover, CD23 was directly activated by PU.1. PU.1 siRNA resulted in downregulation of inflammatory marker expression, but overexpression of CD23 significantly increased the expression of these markers. Our study concluded that CD23 mediates innate immunity against AF in human AMs through activation of PU.1. Therefore, PU.1/CD23 may be a new anti-aspergillosis therapeutic for the treatment of invasive aspergillosis with the deepening of gene therapy and its wide application in the clinic.

scholarly journals Small Noncoding RNAs MTS0997 and MTS1338 Affect the Adaptation and Virulence of Mycobacterium tuberculosis

2021 ◽  
Vol 12 (1) ◽  
pp. 186-195
Author(s):  
Galina Shepelkova ◽  
Vladimir Evstifeev ◽  
Mikhail Averbakch Jr. ◽  
Ilya Sivokozov ◽  
Atadzhan Ergeshov ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Alveolar Macrophages ◽  
Inflammatory Responses ◽  
Primary Cultures ◽  
Mouse Lung ◽  
Infection Model ◽  
Wild Type ◽  
Beneficial Effects ◽  
Human Alveolar Macrophages ◽  
Non Coding Rnas

Tuberculosis (TB) is currently the leading cause of death among bacterial infectious diseases. The spectrum of disease manifestations depends on both host immune responses and the ability of Mycobacterium tuberculosis to resist it. Small non-coding RNAs are known to regulate gene expression; however, their functional role in the relationship of M. tuberculosis with the host is poorly understood. Here, we investigated the effect of small non-coding sRNAs MTS1338 and MTS0997 on M. tuberculosis properties by creating knockout strains. We also assessed the effect of small non-coding RNAs on the survival of wild type and mutant mycobacteria in primary cultures of human alveolar macrophages and the virulence of these strains in a mouse infection model. Wild-type and mutants survived differentially in human alveolar macrophages. Infection of I/St mice with KO M. tuberculosis H37RV strains provided beneficial effects onto major TB phenotypes. We observed attenuated tuberculosis-specific inflammatory responses, including reduced cellular infiltration and decreased granuloma formation in the lungs. Infections caused by KO strains were characterized by significantly lower inflammation of mouse lung tissue and increased survival time of infected animals. Thus, the deletion of MTS0997 and MTS1338 lead to a significant decrease in the virulence of M. tuberculosis.

scholarly journals BALANCE OF PROINFLAMMATORY AND ANTI INFLAMMATORY MARKERS IN ROUTINE HEMODIALYZED PATIENTS (A STUDY OF END-STAGE RENAL FAILURE PATIENTS AT THE DR. SARDJITO HOSPITAL YOGYAKARTA)

2018 ◽  
Vol 24 (2) ◽  
pp. 160
Author(s):  
Ira Puspitawati ◽  
Purwanto A P ◽  
Lisyani B. Suromo
Keyword(s):  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Inflammatory Markers ◽  
Inflammatory Marker ◽  
Enzyme Linked Immunosorbent Assay ◽  
Coronary Syndrome ◽  
Study Results ◽  
Anti Inflammatory ◽  
End Stage ◽  
Spearman Test

Patients with End-Stage Renal Disease (ESRD) tend to have immune imbalance triggered by uremia and Hemodialysis (HD) procedures. Contact between dialysis membrane and blood will cause bio-incompatibility reactions inducing complement activation and production of Reactive Oxygen Species (ROS) as well as proinflammatory cytokines and acute phase protein such as C-Reactive Protein (CRP). Those immune response imbalances will lead to an immunocompromised condition. The objective of this study was to prove the correlation between inflammatory markers (IL-1β, IL-6 and C-reactive proteins) and its anti-inflammatory marker (IL-10) in routine hemodialyzed patients. This is a cross-sectional observational study involving 90 subjects conducted at the Hemodialysis Installation of the Dr. Sardjito Hospital. The inclusion criteria of this study were patients who underwent routine HD procedures, aged between 18 and 65 years-old, having leukocytes count and albumin level within normal limit. The exclusion criteria of this study were patients with Acute Coronary Syndrome (ACS) and malignancies. Levels of IL-1β, IL-6  and IL-10 were measured using Enzyme-Linked Immunosorbent Assay (ELISA), while CRP was measured using highly-sensitive CRP immunoturbidimetry. Statistical analysis was performed by Spearman test. This study results showed correlations between IL-1βand IL-10 (p=0.001, r=0.302), IL-6 and IL-10 (p=0.001, r=0.418) and correlation between CRP and IL-10 (p=0.005, r=0.295). There were also correlations between IL-1β and IL-6 (p=0.029, r=0.232), IL-6 and CRP (p=0.001, r=0.534), but no correlation was found between IL- 1β and CRP (p=0.431, r=0.073). All factors that trigger the secretion of proinflammatory cytokines will trigger the release of anti-inflammatory cytokines, the consequences of anti-inflammatory cytokine secretion will happen minutes after the release of inflammatory cytokines. This study showed that there were correlations between proinflammatory and anti-inflammatory cytokines. Further studies of polymorphism-related cytokines secretion are warranted. 

Hypoxia triggers an antimicrobial pathway in human alveolar macrophages

Pneumologie ◽  
2010 ◽  
Vol 64 (S 03) ◽  
Author(s):  
S Stenger ◽  
D Nickel ◽  
M Wagner ◽  
JH Ficker ◽  
C Schumann
Keyword(s):  
Alveolar Macrophages ◽  
Human Alveolar Macrophages

GDF-15 and neutrophils in patients with heart failure and type 2 diabetes mellitus

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
AA Garganeeva ◽  
EA Kuzheleva ◽  
VA Fedyunina ◽  
VA Aleksandrenko
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Inflammatory Marker ◽  
Study Groups ◽  
Significant Negative Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
National Budget

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was funded by (subject of fundamental scientific research on a state assignment № АААА-А17-117052310073-6 от 23.05.2017 Introduction. Growth differentiation factor-15 (GDF-15) is a biomarker associated with inflammatory processes in the pathogenesis of chronic heart failure (CHF) which expresses in cardiomyocytes under pathological conditions. The relationship between the level of GDF-15 and type 2 diabetes mellitus (T2DM) has also been proven. It is necessary to study GDF-15 in patients with CHF and T2DM. Aim To investigate the association between serum GDF-15 levels in patients with CHF of ischemic etiology and the concentration of the main leukocyte fractions depending on presence or absence of T2DM. Material and methods. The study included 42 patients. The patients were divided into 2 groups. The first group consisted of patients with CHF and T2DM (n = 14). The second group  consisted of patients with CHF without T2DM (n = 28). Determination of GDF-15 concentration was carried out by enzyme-linked immunosorbent assay (BioVendor, Czech Republic). The absolute concentration of lymphocytes, neutrophils, as well as the ratio of neutrophils to lymphocytes in the blood were analyzed. Statistical analysis was performed using the Statistica software (v.10.0). The data were described as a median and interquartile range, the Mann-Whitney test was used to compare them. The correlation analysis was tested using the Spearman"s correlation coefficient. Results and discussion. The average level of the GDF-15 in the study groups was comparable: 2389 (2104; 3375) pg/ml and 2309 (2047; 3014) pg/ml in the first and second groups, respectively (p = 0.6). In the general cohort of CHF patients, the GDF-15 concentration was not correlate with the lymphocytes concentration (r = -0.001, p = 0.95), neutrophils (r = -0.14, p = 0.4) and the ratio of neutrophils to lymphocytes (r = -0.12, p = 0.25). At the same time, in the group of patients with T2DM, a significant negative correlation was revealed between the concentration of GDF-15 in the serum and the concentration of neutrophils (r = -0.6, p = 0.022). While both other analyzed parameters did not demonstrate significant correlations with GDF-15 (p > 0.05). In the group of CHF patients without T2DM, no correlations were found between GDF-15 and the studied parameters, including neutrophils (r = 0.02, p = 0.3). Along with this the median of the neutrophils concentration did not vary among groups (3.5 (2.3; 5.3) vs 3.2 (2.7; 4.1) * 109 / l; p = 0.8). Conclusion The concentration of the inflammatory marker GDF-15 in the blood of patients with CHF in combination with T2DM correlates with the concentration of neutrophils. In the absence of T2DM, no significant correlations were found between GDF-15 and the main leukocyte fractions. The results obtained indicate the possible prospect of using the GDF-15 biomarker in a cohort of patients with CHF in combination with T2DM.

Pathological Alternations of Mediastinal Fat-Associated Lymphoid Cluster and Lung in a Streptozotocin-Induced Diabetic Mouse Model

2020 ◽  
pp. 1-14
Author(s):  
Yaser H.A. Elewa ◽  
Osamu Ichii ◽  
Teppei Nakamura ◽  
Yasuhiro Kon
Keyword(s):  
Endothelial Cells ◽  
Lung Injury ◽  
Mouse Model ◽  
Immune Cells ◽  
Inflammatory Markers ◽  
Inflammatory Marker ◽  
Diabetic Mouse ◽  
Control Group ◽  
Injury Progression

Diabetes is a devastating global health problem and is considered a predisposing factor for lung injury progression. Furthermore, previous reports of the authors revealed the role of mediastinal fat-associated lymphoid clusters (MFALCs) in advancing respiratory diseases. However, no reports concerning the role of MFALCs on the development of lung injury in diabetes have been published. Therefore, this study aimed to examine the correlations between diabetes and the development of MFALCs and the progression of lung injury in a streptozotocin-induced diabetic mouse model. Furthermore, immunohistochemical analysis for immune cells (CD3+ T-lymphocytes, B220+ B-lymphocytes, Iba1+ macrophages, and Gr1+ granulocytes), vessels markers (CD31+ endothelial cells and LYVE-1+ lymphatic vessels “LVs”), and inflammatory markers (TNF-α and IL-5) was performed. In comparison to the control group, the diabetic group showed lung injury development with a significant increase in MFALC size, immune cells, LVs, and inflammatory marker, and a considerable decrease of CD31+ endothelial cells in both lung and MFALCs was observed. Furthermore, the blood glucose level showed significant positive correlations with MFALCs size, lung injury, immune cells, inflammatory markers, and LYVE-1+ LVs in lungs and MFALCs. Thus, we suggest that the development of MFALCs and LVs could contribute to lung injury progression in diabetic conditions.

scholarly journals Duck RIG-I CARD Domain Induces the Chicken IFN-βby Activating NF-κB

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yang Chen ◽  
Zhengyang Huang ◽  
Bin Wang ◽  
Qinming Yu ◽  
Ran Liu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Eukaryotic Expression ◽  
Poly I:C ◽  
Expression Vectors ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Regulatory Domains ◽  
Polycytidylic Acid ◽  
Card Domain ◽  
Inducible Gene

Retinoic acid-inducible gene I- (RIG-I-) like receptors (RLRs) have recently been identified as cytoplasmic sensors for viral RNA. RIG-I, a member of RLRs family, plays an important role in innate immunity. Although previous investigations have proved that RIG-I is absent in chickens, it remains largely unknown whether the chicken can respond to RIG-I ligand. In this study, the eukaryotic expression vectors encoding duRIG-I full length (duck RIG-I, containing all domains), duRIG-I N-terminal (containing the two caspase activation and recruitment domain, CARDs), and duRIG-I C-terminal (containing helicase and regulatory domains) labeled with 6*His tags were constructed successfully and detected by western blotting. Luciferase reporter assay and enzyme-linked immunosorbent assay (ELISA) detected the duRIG-I significantly activated NF-κB and induced the expression of IFN-βwhen polyinosinic-polycytidylic acid (poly[I:C], synthetic double-stranded RNA) challenges chicken embryonic fibroblasts cells (DF1 cells), while the duRIG-I was inactive in the absence of poly[I:C]. Further analysis revealed that the CARDs (duRIG-I-N) induced IFN-βproduction regardless of the presence of poly[I:C], while the CARD-lacking duRIG-I (duRIG-I-C) was not capable of activating downstream signals. These results indicate that duRIG-I CARD domain plays an important role in the induction of IFN-βand provide a basis for further studying the function of RIG-I in avian innate immunity.

scholarly journals Bacillus anthracis Spores Stimulate Cytokine and Chemokine Innate Immune Responses in Human Alveolar Macrophages through Multiple Mitogen-Activated Protein Kinase Pathways

2006 ◽  
Vol 74 (8) ◽  
pp. 4430-4438 ◽  
Author(s):  
Kaushik Chakrabarty ◽  
Wenxin Wu ◽  
J. Leland Booth ◽  
Elizabeth S. Duggan ◽  
K. Mark Coggeshall ◽  
...  
Keyword(s):  
Immune System ◽  
Bacillus Anthracis ◽  
Alveolar Macrophages ◽  
Innate Immune System ◽  
Innate Immune ◽  
Mitogen Activated Protein Kinase ◽  
Tnf Α ◽  
Human Alveolar Macrophages ◽  
Mitogen Activated Protein ◽  
Multiple Signaling

ABSTRACT Contact with the human alveolar macrophage plays a key role in the innate immune response to Bacillus anthracis spores. Because there is a significant delay between the initial contact of the spore with the host and clinical evidence of disease, there appears to be temporary containment of the pathogen by the innate immune system. Therefore, the early macrophage response to Bacillus anthracis exposure is important in understanding the pathogenesis of this disease. In this paper, we studied the initial events after exposure to spores, beginning with the rapid internalization of spores by the macrophages. Spore exposure rapidly activated the mitogen-activated protein kinase signaling pathways extracellular signal-regulated kinase, c-Jun-NH2-terminal kinase, and p38. This was followed by the transcriptional activation of cytokine and primarily monocyte chemokine genes as determined by RNase protection assays. Transcriptional induction is reflected at the translational level, as interleukin-1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) cytokine protein levels were markedly elevated as determined by enzyme-linked immunosorbent assay. Induction of IL-6 and TNF-α, and, to a lesser extent, IL-1α and IL-1β, was partially inhibited by the blockade of individual mitogen-activated protein kinases, while the complete inhibition of cytokine induction was achieved when multiple signaling pathway inhibitors were used. Taken together, these data clearly show activation of the innate immune system in human alveolar macrophages by Bacillus anthracis spores. The data also show that multiple signaling pathways are involved in this cytokine response. This report is the first comprehensive examination of this process in primary human alveolar macrophages.

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