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The Role of Extracellular Vesicles in Cell Communication and Inflammation
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The Role of Extracellular Vesicles in Cell Communication and Inflammation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 6883

Special Issue Editor

Dr. Ilaria Bellezza

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
Interests: oxidative stress and inflammation in cancer; neurodegenerative and retinal diseases; extracellular vesicles in cancer and metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) have been defined as nanosized vesicles that are shed into the extracellular space. First identified in differentiating reticulocytes three decades ago, EVs were thought to be the waste disposal system of cells which aided in the elimination of cellular waste. However, extensive studies over the past two decades have been crucial for introducing a paradigm shift by ascertaining a more sophisticated role of EVs. Intercellular communication is no longer thought to be a consequence of only direct cell–cell contact or secreted factors such as hormone signalling. EVs work by delivering the sequestered cargo to cells in close vicinity, as well as distant sites in the body, regulating pathophysiological processes. Cell death and inflammation are biologically crucial processes in both normal physiology and pathology. These processes are indistinguishably linked, with their effectors modulating the other process. For instance, during an unresolvable infection, the upregulation of specific immune mediators leads to inflammation, causing cell death and tissue damage. EVs have gained considerable interest as mediators of both cell death and inflammation during conditions such as sepsis. This Special Issue welcome articles or reviews on the types of extracellular vesicles known to date and their roles in mediating immune responses leading to cell death and inflammation, with specific focus on sepsis and lung inflammation.

Dr. Ilaria Bellezza
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • inflammation
  • oxidative stress
  • inflammasome
  • extracellular vesicles
  • intercellular communication
  • cell contact
  • cell death

Published Papers (4 papers)

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Research

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17 pages, 7809 KiB  
Article
Stress Conditions Affect the Immunomodulatory Potential of Candida albicans Extracellular Vesicles and Their Impact on Cytokine Release by THP-1 Human Macrophages
by Kamila Kulig, Katarzyna Bednaruk, Elzbieta Rudolphi-Szydło, Anna Barbasz, Ewelina Wronowska, Olga Barczyk-Woznicka, Elzbieta Karnas, Elzbieta Pyza, Ewa Zuba-Surma, Maria Rapala-Kozik and Justyna Karkowska-Kuleta
Int. J. Mol. Sci. 2023, 24(24), 17179; https://doi.org/10.3390/ijms242417179 - 06 Dec 2023
Viewed by 978
Abstract
Human immune cells possess the ability to react complexly and effectively after contact with microbial virulence factors, including those transported in cell-derived structures of nanometer sizes termed extracellular vesicles (EVs). EVs are produced by organisms of all kingdoms, including fungi pathogenic to humans. [...] Read more.
Human immune cells possess the ability to react complexly and effectively after contact with microbial virulence factors, including those transported in cell-derived structures of nanometer sizes termed extracellular vesicles (EVs). EVs are produced by organisms of all kingdoms, including fungi pathogenic to humans. In this work, the immunomodulatory properties of EVs produced under oxidative stress conditions or at host concentrations of CO2 by the fungal pathogen Candida albicans were investigated. The interaction of EVs with human pro-monocytes of the U-937 cell line was established, and the most notable effect was attributed to oxidative stress-related EVs. The immunomodulatory potential of tested EVs against human THP-1 macrophages was verified using cytotoxicity assay, ROS-production assay, and the measurement of cytokine production. All fungal EVs tested did not show a significant cytotoxic effect on THP-1 cells, although a slight pro-oxidative impact was indicated for EVs released by C. albicans cells grown under oxidative stress. Furthermore, for all tested types of EVs, the pro-inflammatory properties related to increased IL-8 and TNF-α production and decreased IL-10 secretion were demonstrated, with the most significant effect observed for EVs released under oxidative stress conditions. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Cell Communication and Inflammation)
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18 pages, 2986 KiB  
Article
Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation
by Emilia Nunzi, Letizia Mezzasoma, Ilaria Bellezza, Teresa Zelante, Pierluigi Orvietani, Giuliana Coata, Irene Giardina, Krizia Sagini, Giorgia Manni, Alessandro Di Michele, Marco Gargaro, Vincenzo N. Talesa, Gian Carlo Di Renzo, Francesca Fallarino and Rita Romani
Int. J. Mol. Sci. 2023, 24(3), 2527; https://doi.org/10.3390/ijms24032527 - 28 Jan 2023
Cited by 4 | Viewed by 1643
Abstract
In pregnancy, human amniotic fluid extracellular vesicles (HAF-EVs) exert anti-inflammatory effects on T cells and on monocytes, supporting their immunoregulatory roles. The specific mechanisms are still not completely defined. The aim of this study was to investigate the ability of HAF-EVs, isolated from [...] Read more.
In pregnancy, human amniotic fluid extracellular vesicles (HAF-EVs) exert anti-inflammatory effects on T cells and on monocytes, supporting their immunoregulatory roles. The specific mechanisms are still not completely defined. The aim of this study was to investigate the ability of HAF-EVs, isolated from pregnant women who underwent amniocentesis and purified by gradient ultracentrifugation, to affect inflammasome activation in the human monocytes. Proteomic studies revealed that HAF-EV samples expressed several immunoregulatory molecules as well as small amounts of endotoxin. Surprisingly, metagenomic analysis shows the presence of specific bacterial strain variants associated with HAF-EVs as potential sources of the endotoxin. Remarkably, we showed that a single treatment of THP-1 cells with HAF-EVs triggered inflammasome activation, whereas the same treatment followed by LPS and ATP sensitization prevented inflammasome activation, a pathway resembling monocyte refractories. A bioinformatics analysis of microbiota-HAF-EVs functional pathways confirmed the presence of enzymes for endotoxin biosynthesis as well as others associated with immunoregulatory functions. Overall, these data suggest that HAF-EVs could serve as a source of the isolation of a specific microbiota during early pregnancy. Moreover, HAF-EVs could act as a novel system to balance immune training and tolerance by modulating the inflammasome in monocytes or other cells. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Cell Communication and Inflammation)
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20 pages, 3118 KiB  
Article
Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia
by Anny Waloski Robert, Bruna Hilzendeger Marcon, Addeli Bez Batti Angulski, Sharon de Toledo Martins, Amanda Leitolis, Marco Augusto Stimamiglio, Alexandra Cristina Senegaglia, Alejandro Correa and Lysangela Ronalte Alves
Int. J. Mol. Sci. 2022, 23(17), 10066; https://doi.org/10.3390/ijms231710066 - 02 Sep 2022
Cited by 4 | Viewed by 1749
Abstract
Endothelial-like cells may be obtained from CD133+ mononuclear cells isolated from human umbilical cord blood (hUCB) and expanded using endothelial-inducing medium (E-CD133 cells). Their use in regenerative medicine has been explored by the potential not only to form vessels but also by [...] Read more.
Endothelial-like cells may be obtained from CD133+ mononuclear cells isolated from human umbilical cord blood (hUCB) and expanded using endothelial-inducing medium (E-CD133 cells). Their use in regenerative medicine has been explored by the potential not only to form vessels but also by the secretion of bioactive elements. Extracellular vesicles (EVs) are prominent messengers of this paracrine activity, transporting bioactive molecules that may guide cellular response under different conditions. Using RNA-Seq, we characterized the miRNA content of EVs derived from E-CD133 cells cultivated under normoxia (N-EVs) and hypoxia (H-EVs) and observed that changing the O2 status led to variations in the selective loading of miRNAs in the EVs. In silico analysis showed that among the targets of differentially loaded miRNAs, there are transcripts involved in pathways related to cell growth and survival, such as FoxO and HIF-1 pathways. The data obtained reinforce the pro-regenerative potential of EVs obtained from E-CD133 cells and shows that fine tuning of their properties may be regulated by culture conditions. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Cell Communication and Inflammation)
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Review

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22 pages, 1130 KiB  
Review
Looking to the Future of the Role of Macrophages and Extracellular Vesicles in Neuroinflammation in ALS
by Elisabetta Carata, Marco Muci, Simona Di Giulio, Stefania Mariano and Elisa Panzarini
Int. J. Mol. Sci. 2023, 24(14), 11251; https://doi.org/10.3390/ijms241411251 - 08 Jul 2023
Cited by 5 | Viewed by 2026
Abstract
Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and disease progression is attracting research interest. Activated CNS (Central [...] Read more.
Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and disease progression is attracting research interest. Activated CNS (Central Nervous System) glial cells, proinflammatory peripheral and infiltrated T lymphocytes and monocytes/macrophages, as well as the immunoreactive molecules they release, represent the active players for the role of immune dysregulation enhancing neuroinflammation. The crosstalk between the peripheral and CNS immune cells significantly correlates with the survival of ALS patients since the modification of peripheral macrophages can downregulate inflammation at the periphery along the nerves and in the CNS. As putative vehicles for misfolded protein and inflammatory mediators between cells, extracellular vesicles (EVs) have also drawn particular attention in the field of ALS. Both CNS and peripheral immune cells release EVs, which are able to modulate the behavior of neighboring recipient cells; unfortunately, the mechanisms involved in EVs-mediated communication in neuroinflammation remain unclear. This review aims to synthesize the current literature regarding EV-mediated cell-to-cell communication in the brain under ALS, with a particular point of view on the role of peripheral macrophages in responding to inflammation to understand the biological process and exploit it for ALS management. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Cell Communication and Inflammation)
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