The role of mononuclear phagocytes in HTLV-III/LAV infection

Science ◽  
1986 ◽  
Vol 233 (4760) ◽  
pp. 215-219 ◽  
Author(s):  
S Gartner ◽  
P Markovits ◽  
D. Markovitz ◽  
M. Kaplan ◽  
R. Gallo ◽  
...  
Keyword(s):  
Mononuclear Phagocytes

scholarly journals Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321731
Author(s):  
Dominik Aschenbrenner ◽  
Maria Quaranta ◽  
Soumya Banerjee ◽  
Nicholas Ilott ◽  
Joanneke Jansen ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Personalised Medicine ◽  
Mononuclear Phagocytes ◽  
Cytokine Network ◽  
Peripheral Blood Mononuclear ◽  
Transcriptional Signature ◽  
Inflammatory Monocytes ◽  
Transcriptomic Signature ◽  
Inflammatory Bowel

ObjectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.DesignWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.ResultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.ConclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

scholarly journals Secretome Profiling of Atlantic Salmon Head Kidney Leukocytes Highlights the Role of Phagocytes in the Immune Response to Soluble β-Glucan

2021 ◽  
Vol 12 ◽  
Author(s):  
Dimitar B. Iliev ◽  
Guro Strandskog ◽  
Mehrdad Sobhkhez ◽  
Jack A. Bruun ◽  
Jorunn B. Jørgensen
Keyword(s):  
Immune System ◽  
Atlantic Salmon ◽  
Primary Cultures ◽  
Head Kidney ◽  
Cell Types ◽  
Mononuclear Phagocytes ◽  
Immunostimulatory Activity ◽  
Complement Receptor 3 ◽  
Bacteria And Fungi

β‐Glucans (BG) are glucose polymers which are produced in bacteria and fungi but not in vertebrate organisms. Being recognized by phagocytic leukocytes including macrophages and neutrophils through receptors such as dectin-1 and Complement receptor 3 (CR3), the BG are perceived by the innate immune system of vertebrates as foreign substances known as Pathogen Associated Molecular Patterns (PAMPs). The yeast-derived BG has been recognized for its potent biological activity and it is used as an immunomodulator in human and veterinary medicine. The goal of the current study was to characterize the immunostimulatory activity of soluble yeast BG in primary cultures of Atlantic salmon (Salmo salar) head kidney leukocytes (HKLs) in which phagocytic cell types including neutrophils and mononuclear phagocytes predominate. The effect of BG on the secretome of HKL cultures, including secretion of extracellular vesicles (EVs) and soluble protein55s was characterized through western blotting and mass spectrometry. The results demonstrate that, along with upregulation of proinflammatory genes, BG induces secretion of ubiquitinated proteins (UbP), MHCII-containing EVs from professional antigen presenting cells as well as proteins derived from granules of polymorphonuclear granulocytes (PMN). Among the most abundant proteins identified in BG-induced EVs were beta-2 integrin subunits, including CD18 and CD11 homologs, which highlights the role of salmon granulocytes and mononuclear phagocytes in the response to soluble BG. Overall, the current work advances the knowledge about the immunostimulatory activity of yeast BG on the salmon immune system by shedding light on the effect of this PAMP on the secretome of salmon leukocytes.

Multinucleated rat alveolar macrophages express functional receptors for calcitonin

1991 ◽  
Vol 261 (6) ◽  
pp. F1026-F1032 ◽  
Author(s):  
A. Vignery ◽  
M. J. Raymond ◽  
H. Y. Qian ◽  
F. Wang ◽  
S. A. Rosenzweig
Keyword(s):  
Plasma Membrane ◽  
Alveolar Macrophages ◽  
Giant Cells ◽  
Mononuclear Phagocytes ◽  
Inflammatory Reactions ◽  
Calcitonin Gene ◽  
Novel Model

The fusion of mononuclear phagocytes occurs spontaneously in vivo and leads to the differentiation of either multinucleated giant cells or osteoclasts in chronic inflammatory sites or in bone, respectively. Although osteoclasts are responsible for resorbing bone, the functional role of giant cells in chronic inflammatory reactions and tumors remains poorly understood. We recently reported that the plasma membrane of multinucleated macrophages is, like that of osteoclasts, enriched in Na-K-adenosinetriphosphatases (ATPases). We also observed that the localization of their Na-K-ATPases is restricted to the nonadherent domain of the plasma membrane of cells both in vivo and in vitro, thus imposing a functional polarity on their organization. By following this observation, we wished to investigate whether these cells also expressed, like osteoclasts, functional receptors for calcitonin (CT). To this end, alveolar macrophages were fused in vitro, and both their structural and functional association with CT was analyzed and compared with those of mononucleated peritoneal and alveolar macrophages. Evidence is presented that multinucleated alveolar macrophages express a high copy number of functional receptors for CT. Our results also indicate that alveolar macrophages, much like peritoneal, express functional receptors for calcitonin gene-related peptide. It is suggested that multinucleated rat alveolar macrophages offer a novel model system to study CT receptors and that calcitonin may control local immune reactions where giant cells differentiate.

Role of Mononuclear Phagocytes in the Pathogenesis of Human Immunodeficiency Virus Infection

1990 ◽  
Vol 8 (1) ◽  
pp. 169-194 ◽  
Author(s):  
Monte S. Meltzer ◽  
Donald R. Skillman ◽  
Peter J. Gomatos ◽  
D. Chester Kalter ◽  
Howard E. Gendelman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Human Immunodeficiency Virus Infection ◽  
Mononuclear Phagocytes ◽  
Immunodeficiency Virus

Akt Activation Regulates Macrophage Survival and Differentiation: Role of M-CSF and Endogenous ROS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2208-2208
Author(s):  
Yijie Wang ◽  
Mandy M. Zeigler ◽  
Greg K. Lam ◽  
Melissa G. Hunter ◽  
Tim D. Eubank ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Survival ◽  
Kinase Inhibitors ◽  
Critical Role ◽  
Annexin V ◽  
Mononuclear Phagocytes ◽  
Ros Generation ◽  
Blood Monocytes ◽  
Human Alveolar Macrophage

Abstract Previous reports from our laboratory showed M-CSF promotes PI 3-kinase activation resulting in the production of reactive oxygen species (ROS) and PI 3-kinase inhibitors, and the antioxidants diphenyleneiodonium (DPI) and n-acetyl cysteine (NAC) suppressed M-CSF-stimulated Erk activation. In this study, we hypothesized that M-CSF-induced generation of ROS affected Akt1 activation and sought to define the role of Akt1 in monocyte/macrophage survival and differentiation. We found that the production of ROS following M-CSF-treatment was inhibited by the antioxidant DPI. The addition of either DPI or NAC to the monocytes in the presence of M-CSF resulted in decrease cell survival as measured by Annexin V/PI and DNA fragmentation. In the cells treated with the antioxidants, there was a reduction in pAKT protein levels compared to M-CSF alone treatment suggesting that ROS contributed to Akt activity and cell survival. Macrophages from p47phox −/− mice, lacking a key component of the NADPH oxidase complex required for ROS generation were examined for M-CSF-induced survival and Akt1 activation. Bone marrow macrophages from p47phox −/ − mice and wild type (WT) littermates were isolated and differentiated in RPMI-1640 medium in the presence of 20 ng/ml of M-CSF for 5 days. We observed a reduction in Akt1 phosphorylation, cellular survival and increase in apoptosis measured by Annexin V/PI staining in p47phox −/ − macrophages compared to WT controls. Since macrophages from the p47phox−/− mice had reduced Akt1 activity and cell survival to M-CSF stimulation, we next wanted to independently evaluate the role of Akt in macrophage survival and differentiation. We therefore examined macrophages from mice that had targeted expression of activated Akt1 (Myr-Akt1) in mononuclear phagocytes. Bone marrow from Myr-Akt1 mice and (WT) littermates was isolated and cultured in the presence of 20 ng/ml of M-CSF for 5 days. We found that Myr-Akt1 cells had enhanced survival and reduced apoptosis versus WT cells. Interestingly, Myr-Akt1 mice had normal circulating numbers of monocytes, but had splenomegaly and increased numbers of mature macrophages in their spleens by CD68 staining. Since the expression of Myr-Akt1 in BMM enhanced cell survival, we were interested in the effect in human monocytes. Peripheral blood monocytes (PBM) were transiently transfected with Myr-Akt1 constructs. We observed a decrease in Annexin V/PI staining indicating promotion of cell survival in PBM expressing Myr-Akt compared to untransfected PBM. Since Akt1 appeared to be important for macrophage survival/differentiation, we examined its contribution in human alveolar macrophage homeostasis and found that freshly isolated macrophages had constitutive Akt1 activity and had increased levels of Akt1 protein. This data support a critical role for Akt1 in macrophage differentiation in mice. Together, our findings may provide insight in the pathogenesis of monocyte/macrophage homeostasis.

scholarly journals Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation

2017 ◽  
Vol 214 (4) ◽  
pp. 905-917 ◽  
Author(s):  
Yochai Wolf ◽  
Anat Shemer ◽  
Michal Polonsky ◽  
Mor Gross ◽  
Alexander Mildner ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mononuclear Phagocytes ◽  
Autoimmune Encephalomyelitis ◽  
Wild Type Counterpart ◽  
And Function ◽  
Necrosis Factor ◽  
Experimental Autoimmune

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function.

scholarly journals Role of the NF-κB Signaling Pathway and κB cis-Regulatory Elements on the IRF-1 and iNOS Promoter Regions in Mycobacterial Lipoarabinomannan Induction of Nitric Oxide

2003 ◽  
Vol 71 (3) ◽  
pp. 1442-1452 ◽  
Author(s):  
Kristin R. Morris ◽  
Ryan D. Lutz ◽  
Hyung-Seok Choi ◽  
Tetsu Kamitani ◽  
Kathryn Chmura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Host Defense ◽  
Regulatory Elements ◽  
Mononuclear Phagocytes ◽  
Intact Cells ◽  
Ifn Γ ◽  
Flanking Region ◽  
Mycobacterial Cell Wall

ABSTRACT Nitric oxide (NO·) produced by inducible nitric oxide synthase (iNOS) is an important host defense molecule against Mycobacterium tuberculosis in mononuclear phagocytes. The objective of this study was to determine the role of the IκBα kinase-nuclear factor κB (IKK-NF-κB) signaling pathway in the induction of iNOS and NO· by a mycobacterial cell wall lipoglycan known as mannose-capped lipoarabinomannan (ManLAM) in mouse macrophages costimulated with gamma interferon (IFN-γ). NF-κB was activated by ManLAM as shown by electrophoretic mobility shift assay, by immunofluorescence of translocated NF-κB in intact cells, and by a reporter gene driven by four NF-κB-binding elements. Transduction of an IκBα mutant (Ser32/36Ala) significantly inhibited NO· expression induced by IFN-γ plus ManLAM. An activated SCF complex, a heterotetramer (Skp1, Cul-1, β-TrCP [F-box protein], and ROC1) involved with ubiquitination, is also required for iNOS-NO· induction. Two NF-κB-binding sites (κBI and κBII) present on the 5′-flanking region of the iNOS promoter bound ManLAM-induced NF-κB similarly. By use of reporter constructs in which one or both sites are mutated, both NF-κB-binding positions were essential in iNOS induction by IFN-γ plus ManLAM. IFN-γ-induced activation of the IRF-1 transcriptional complex is a necessary component in host defense against tuberculosis. Although the 5′-flanking region of the IRF-1 promoter contains an NF-κB-binding site and ManLAM-induced NF-κB also binds to this site, ManLAM was unable to induce IRF-1 expression. The influence of mitogen-activated protein kinases on IFN-γ plus ManLAM induction of iNOS-NO· is not due to any effects on ManLAM induction of NF-κB.

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