scholarly journals Pathogenic Stress Induces Human Monocyte to Express an Extracellular Web of Tunneling Nanotubes

2021 ◽  
Vol 12 ◽  
Author(s):  
Michal Shahar ◽  
Auryan Szalat ◽  
Haim Rosen
Keyword(s):  
Intercellular Communication ◽  
Environmental Changes ◽  
Imaging System ◽  
Human Monocyte ◽  
Cell Types ◽  
Similar Response ◽  
Human Monocytes ◽  
Tunneling Nanotubes ◽  
Membrane Components

Actin-based tunneling nanotubes are a means of intercellular communication between remote cells. In the last decade, this type of nanotube was described in a wide variety of cell types and it became widely accepted that communication through these nanotubes is related to response to environmental changes. Few reports, however, are available regarding the expression of similar nanotubes in vivo or in primary cells. Moreover, the functional significance of this intercellular communication for health and disease is largely unknown. In this context, and as a first step in unraveling these questions, we examined the formation of similar nanotubes in primary peripheral human monocytes. To that end, we combined the use of a live cell imaging system along with advanced methods of fluorescent and scanning electron microscopy. This experimental approach reveals for the first time that the bacterial lipopolysaccharide endotoxin induces a transient expression of an unexpected abundance of actin-based tunneling nanotubes associated with vesicles. In addition, it was found that a similar response can be achieved by treating human monocytes with various bacterial and yeast membrane components, as well as with a viral component analog. In all these cases, this response is mediated by distinct complexes of toll-like receptors. Therefore, we suggest that the observed phenomena are related to a broad type of monocyte pathogen response, and raise the possibility that the phenomena described above may be involved in many clinical situations related to inflammation as a new topic of study.

scholarly journals Patient-derived Glioblastoma Stem cells transfer mitochondria through Tunneling Nanotubes in Tumor Organoids

2020 ◽  
Author(s):  
Giulia Pinto ◽  
Inés Saenz de Santa Maria ◽  
Patricia Chastagner ◽  
Emeline Perthame ◽  
Caroline Delmas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intercellular Communication ◽  
Brain Cancer ◽  
Therapy Resistance ◽  
Malignant Phenotype ◽  
Tunneling Nanotubes ◽  
Mitochondria Transfer ◽  
First Time ◽  
Tumor Organoids

Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSLCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor’s features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking.

Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1694-1702 ◽  
Author(s):  
Christine Chauveau ◽  
Séverine Rémy ◽  
Pierre Joseph Royer ◽  
Marcelo Hill ◽  
Séverine Tanguy-Royer ◽  
...  
Keyword(s):  
Immune Responses ◽  
Heme Oxygenase ◽  
Human Monocyte ◽  
Cell Types ◽  
Interleukin 10 ◽  
Dendritic Cell Maturation ◽  
Heme Oxygenase 1 ◽  
Intracellular Enzyme

Abstract Heme oxygenase-1 (HO-1) is an intracellular enzyme that degrades heme and inhibits immune responses and inflammation in vivo. In most cell types, HO-1 is inducible by inflammatory stimuli and oxidative stress. Here we demonstrate that human monocyte-derived immature dendritic cells (iDCs) and several but not all freshly isolated rat splenic DC subsets and rat bone marrow-derived iDCs, spontaneously express HO-1. HO-1 expression drastically decreases during human and rat DC maturation induced in vitro. In human tissues, iDCs also express HO-1, whereas mature DCs do not. Induction of HO-1 expression with cobalt protoporphyrin (CoPP) in human and rat DCs inhibits lipopolysaccharide (LPS)-induced phenotypic maturation and secretion of proinflammatory cytokines, resulting in the inhibition of alloreactive T-cell proliferation. CoPP-treated DCs, however, retain the ability to produce the anti-inflammatory cytokine interleukin 10 (IL-10). Reactive oxygen species induced by LPS in DCs were inhibited by induction of HO-1. In conclusion, we identify, for the first time, the capacity of HO-1 to block maturation of DCs and to inhibit proinflammatory and allogeneic immune responses while preserving IL-10 production. This novel immune function for HO-1 may be of interest for the inhibition of immune responses in autoimmune diseases, transplantation, and other conditions involving activation of the immune system. (Blood. 2005;106:1694-1702)

scholarly journals Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment

2021 ◽  
Author(s):  
Margaret E Maes ◽  
Gabriele M Wögenstein ◽  
Gloria Colombo ◽  
Raquel Casado-Polanco ◽  
Sandra Siegert
Keyword(s):  
Environmental Changes ◽  
Genetic Material ◽  
Plexiform Layer ◽  
Cell Types ◽  
Transduction Efficiency ◽  
Heparin Binding ◽  
Future Studies ◽  
Distinct Cell ◽  
Transgene Delivery

AbstractAdeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette.Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.

scholarly journals Cholera Toxin and Heat-Labile Enterotoxin Activate Human Monocyte-Derived Dendritic Cells and Dominantly Inhibit Cytokine Production through a Cyclic AMP-Dependent Pathway

2002 ◽  
Vol 70 (10) ◽  
pp. 5533-5539 ◽  
Author(s):  
Kenneth C. Bagley ◽  
Sayed F. Abdelwahab ◽  
Robert G. Tuskan ◽  
Timothy R. Fouts ◽  
George K. Lewis
Keyword(s):  
Dendritic Cells ◽  
Cyclic Amp ◽  
Cholera Toxin ◽  
Human Monocyte ◽  
Cell Types ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Heat Labile

ABSTRACT Cholera toxin (CT) and heat-labile enterotoxin (LT) are powerful mucosal adjuvants whose cellular targets and mechanism of action are unknown. There is emerging evidence that dendritic cells (DC) are one of the principal cell types that mediate the adjuvant effects of these toxins in vivo. Here we investigate the effects of CT and LT on the maturation of human monocyte-derived DC (MDDC) in vitro. We found that an enzymatically active A domain is necessary for both CT and LT to induce the maturation of MDDC and that this activation is strictly cyclic AMP (cAMP) dependent. ADP-ribosylation-defective derivatives of these toxins failed to induce maturation of MDDC, whereas dibutyryl-cyclic-3′,5′-AMP and Forskolin mimic the maturation of MDDC induced by CT and LT. In addition, an inhibitor of cAMP-dependent kinases, Rp-8-Br-cAMPs, blocked the ability of CT, LT, and Forskolin to activate MDDC. CT, LT, dibutyryl-cyclic-3′,5′-AMP, and Forskolin also dominantly inhibit interleukin 12 and tumor necrosis factor alpha production by MDDC in the presence of saturating concentrations of lipopolysaccharide. Taken together, these results show that the effects of CT and LT on MDDC are mediated by cAMP.

scholarly journals Connecting different heart diseases through intercellular communication

Biology Open ◽  
2021 ◽  
Vol 10 (9) ◽  
Author(s):  
Tania Martins-Marques
Keyword(s):  
Communication Networks ◽  
Intercellular Communication ◽  
Heart Diseases ◽  
Clinical Manifestations ◽  
Cell Communication ◽  
Cell Types ◽  
Mediated Communication ◽  
Tunneling Nanotubes ◽  
Organelle Transfer ◽  
Heart Beating

ABSTRACT Well-orchestrated intercellular communication networks are pivotal to maintaining cardiac homeostasis and to ensuring adaptative responses and repair after injury. Intracardiac communication is sustained by cell–cell crosstalk, directly via gap junctions (GJ) and tunneling nanotubes (TNT), indirectly through the exchange of soluble factors and extracellular vesicles (EV), and by cell–extracellular matrix (ECM) interactions. GJ-mediated communication between cardiomyocytes and with other cardiac cell types enables electrical impulse propagation, required to sustain synchronized heart beating. In addition, TNT-mediated organelle transfer has been associated with cardioprotection, whilst communication via EV plays diverse pathophysiological roles, being implicated in angiogenesis, inflammation and fibrosis. Connecting various cell populations, the ECM plays important functions not only in maintaining the heart structure, but also acting as a signal transducer for intercellular crosstalk. Although with distinct etiologies and clinical manifestations, intercellular communication derailment has been implicated in several cardiac disorders, including myocardial infarction and hypertrophy, highlighting the importance of a comprehensive and integrated view of complex cell communication networks. In this review, I intend to provide a critical perspective about the main mechanisms contributing to regulate cellular crosstalk in the heart, which may be considered in the development of future therapeutic strategies, using cell-based therapies as a paradigmatic example. This Review has an associated Future Leader to Watch interview with the author.

HIV-1 Nef activates STAT1 in human monocytes/macrophages through the release of soluble factors

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2752-2761 ◽  
Author(s):  
Maurizio Federico ◽  
Zulema Percario ◽  
Eleonora Olivetta ◽  
Gianna Fiorucci ◽  
Claudia Muratori ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Intracellular Signaling ◽  
Human Monocyte ◽  
Binding Activity ◽  
Human Monocytes ◽  
Soluble Factors ◽  
In Vivo Models ◽  
Wide Range ◽  
Hiv 1

AbstractMonocytes/macrophages play a predominant role in the immunologic network by secreting and reacting to a wide range of soluble factors. Human immunodeficiency virus (HIV) infection leads to deep immunologic dysfunctions, also as a consequence of alterations in the pattern of cytokine release. Recent studies on in vivo models demonstrated that the expression of HIV Nef alone mimics many pathogenetic effects of HIV infection. In particular, Nef expression in monocytes/macrophages has been correlated with remarkable modifications in the pattern of secreted soluble factors, suggesting that the interaction of Nef with monocytes/macrophages plays a role in the pathogenesis of acquired immunodeficiency syndrome (AIDS). This study sought to define possible alterations in intracellular signaling induced by Nef in monocytes/macrophages. Results demonstrate that HIV-1 Nef specifically activates both α and β isoforms of the signal transducer and activator of transcription 1 (STAT1). This was observed both by infecting human monocyte-derived macrophages (MDMs) with HIV-1 deletion mutants, and by exploiting the ability of MDMs to internalize soluble, recombinant Nef protein (rNef). STAT1-α activation occurs on phosphorylation of both C-terminal Tyr701 and Ser727 and leads to a strong binding activity. Nef-dependent STAT1 activation is followed by increased expression of both STAT1 and interferon regulatory factor-1, a transcription factor transcriptionally regulated by STAT1 activation. It was also established that Nef-induced STAT1- α/β activation occurs through the secretion of soluble factors. Taken together, the results indicate that HIV-1 Nef could interfere with STAT1-governed intracellular signaling in human monocytes/macrophages.

scholarly journals Regulation of the maturation of human monocytes into immunosuppressive macrophages

2017 ◽  
Vol 1 (26) ◽  
pp. 2510-2519 ◽  
Author(s):  
Defne Bayik ◽  
Debra Tross ◽  
Lydia A. Haile ◽  
Daniela Verthelyi ◽  
Dennis M. Klinman
Keyword(s):  
P38 Mapk ◽  
Human Monocyte ◽  
Human Monocytes ◽  
Toll Like Receptor ◽  
Macrophage Differentiation ◽  
Key Points ◽  
Toll Like Receptor 2

Key Points NF-κB and Akt regulate human monocyte into macrophage differentiation; p38 MAPK and PTGS2 promote the generation of suppressive macrophage. The Toll-like receptor 2/1 agonist PAM3 induces human monocytes to mature into immunosuppressive macrophages in vitro and in vivo.

scholarly journals Specialized Intercellular Communications via Cytonemes and Nanotubes

2018 ◽  
Vol 34 (1) ◽  
pp. 59-84 ◽  
Author(s):  
Yukiko M. Yamashita ◽  
Mayu Inaba ◽  
Michael Buszczak
Keyword(s):  
Intercellular Communication ◽  
Cell Types ◽  
Current Understanding ◽  
Cellular Interactions ◽  
Thin Membrane ◽  
Tunneling Nanotubes ◽  
Membrane Protrusions ◽  
Intercellular Communications ◽  
And Diffusion

In recent years, thin membrane protrusions such as cytonemes and tunneling nanotubes have emerged as a novel mechanism of intercellular communication. Protrusion-based cellular interactions allow for specific communication between participating cells and have a distinct spectrum of advantages compared to secretion- and diffusion-based intercellular communication. Identification of protrusion-based signaling in diverse systems suggests that this mechanism is a ubiquitous and prevailing means of communication employed by many cell types. Moreover, accumulating evidence indicates that protrusion-based intercellular communication is often involved in pathogenesis, including cancers and infections. Here we review our current understanding of protrusion-based intercellular communication.

scholarly journals Patient-derived Glioblastoma Stem cells transfer mitochondria through Tunneling Nanotubes in Tumor Organoids

2020 ◽  
Author(s):  
Giulia Pinto ◽  
Inés Saenz-de-Santa-Maria ◽  
Patricia Chastagner ◽  
Emeline Perthame ◽  
Caroline Delmas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intercellular Communication ◽  
Brain Cancer ◽  
Therapy Resistance ◽  
Malignant Phenotype ◽  
Tunneling Nanotubes ◽  
Mitochondria Transfer ◽  
First Time ◽  
Tumor Organoids

AbstractGlioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSLCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor’s features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking.

scholarly journals Exosomes for Intramyocardial Intercellular Communication

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Elisabetta Cervio ◽  
Lucio Barile ◽  
Tiziano Moccetti ◽  
Giuseppe Vassalli
Keyword(s):  
Intercellular Communication ◽  
Cardiac Fibroblasts ◽  
Cell Types ◽  
Cardiac Progenitor Cells ◽  
Adaptive Responses ◽  
Regulate Gene Expression ◽  
Cells Of Origin ◽  
Different Cell Types ◽  
Regulate Gene

Cross-talk between different cell types plays central roles both in cardiac homeostasis and in adaptive responses of the heart to stress. Cardiomyocytes (CMs) send biological messages to the other cell types present in the heart including endothelial cells (ECs) and fibroblasts. In turn, CMs receive messages from these cells. Recent evidence has now established that exosomes, nanosized secreted extracellular vesicles, are crucial mediators of such messages. CMs, ECs, cardiac fibroblasts, and cardiac progenitor cells (CPCs) release exosomes carrying nonrandom subsets of proteins, lipids, and nucleic acids present in their cells of origin. Exosomes secreted from CMs are internalized by fibroblasts and regulate gene expression in these cells as well as in ECs. CPC-derived exosomes protect CMs against apoptosis while also stimulating angiogenesis. They are rich in cardioprotective and proangiogenic microRNAs such as miR-146, miR-210, and miR-132. When injected into infracted heartsin vivo, CPC-derived exosomes reduce infarct size and improve cardiac function. Thus, exosomes are emerging both as key mediators of intercellular communication in the heart and as therapeutic candidates for heart disease.

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