Modulating Cytokine Production via Select Packaging and Secretion From Extracellular Vesicles

Barnes, Betsy J.; Somerville, Carter

doi:10.3389/fimmu.2020.01040

Cited by 61 publications

(58 citation statements)

References 131 publications

(119 reference statements)

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“…For instance, cellular activation has been shown to yield higher levels of EV secretion compared to resting cells. This upregulation in EV trafficking has been observed to occur in parallel with increases in intracellular calcium (Ca + ) levels and cytoskeletal remodeling [ 227 , 228 ]. Therefore, the control of intracellular calcium levels may allow for the control of EV release.…”

Section: Treatments Used To Modulate Ev Biogenesis Release and Umentioning

confidence: 99%

Extracellular Vesicles in HTLV-1 Communication: The Story of an Invisible Messenger

Sharif

Pinto

Mensah

et al. 2020

Viruses

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Human T-cell lymphotropic virus type 1 (HTLV-1) infects 5–10 million people worldwide and is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as other inflammatory diseases. A major concern is that the most majority of individuals with HTLV-1 are asymptomatic carriers and that there is limited global attention by health care officials, setting up potential conditions for increased viral spread. HTLV-1 transmission occurs primarily through sexual intercourse, blood transfusion, intravenous drug usage, and breast feeding. Currently, there is no cure for HTLV-1 infection and only limited treatment options exist, such as class I interferons (IFN) and Zidovudine (AZT), with poor prognosis. Recently, small membrane-bound structures, known as extracellular vesicles (EVs), have received increased attention due to their potential to carry viral cargo (RNA and proteins) in multiple pathogenic infections (i.e., human immunodeficiency virus type I (HIV-1), Zika virus, and HTLV-1). In the case of HTLV-1, EVs isolated from the peripheral blood and cerebral spinal fluid (CSF) of HAM/TSP patients contained the viral transactivator protein Tax. Additionally, EVs derived from HTLV-1-infected cells (HTLV-1 EVs) promote functional effects such as cell aggregation which enhance viral spread. In this review, we present current knowledge surrounding EVs and their potential role as immune-modulating agents in cancer and other infectious diseases such as HTLV-1 and HIV-1. We discuss various features of EVs that make them prime targets for possible vehicles of future diagnostics and therapies.

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Section: Treatments Used To Modulate Ev Biogenesis Release and Umentioning

confidence: 99%

Extracellular Vesicles in HTLV-1 Communication: The Story of an Invisible Messenger

Sharif

Pinto

Mensah

et al. 2020

Viruses

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“…They may be released from damaged or stressed cells and carry proteins, pathogen-associated and damage-associated molecular patterns, lipids and miRNA, which are encapsulated and thus protected from degrading enzymes [ 14 ]. Cytokines may be selectively sorted to EVs and act as signals to regulate and propagate the immune and inflammatory response [ 15 ]. EV-associated cytokines are different from those released in a soluble form by cells of the same type [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study

et al. 2020

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Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of unknown etiology lasting for a minimum of 6 months but usually for many years, with features including fatigue, cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Dysregulation of cytokine signaling could give rise to many of these symptoms. Cytokines are present in both plasma and extracellular vesicles, but little investigation of EVs in ME/CFS has been reported. Therefore, we aimed to characterize the content of extracellular vesicles (EVs) isolated from plasma (including circulating cytokine/chemokine profiling) from individuals with ME/CFS and healthy controls. Methods We included 35 ME/CFS patients and 35 controls matched for age, sex and BMI. EVs were enriched from plasma by using a polymer-based precipitation method and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM) and immunoblotting. A 45-plex immunoassay was used to determine cytokine levels in both plasma and isolated EVs from a subset of 19 patients and controls. Linear regression, principal component analysis and inter-cytokine correlations were analyzed. Results ME/CFS individuals had significantly higher levels of EVs that ranged from 30 to 130 nm in size as compared to controls, but the mean size for total extracellular vesicles did not differ between groups. The enrichment of typical EV markers CD63, CD81, TSG101 and HSP70 was confirmed by Western blot analysis and the morphology assessed by TEM showed a homogeneous population of vesicles in both groups. Comparison of cytokine concentrations in plasma and isolated EVs of cases and controls yielded no significant differences. Cytokine-cytokine correlations in plasma revealed a significant higher number of interactions in ME/CFS cases along with 13 inverse correlations that were mainly driven by the Interferon gamma-induced protein 10 (IP-10), whereas in the plasma of controls, no inverse relationships were found across any of the cytokines. Network analysis in EVs from controls showed 2.5 times more significant inter-cytokine interactions than in the ME/CFS group, and both groups presented a unique negative association. Conclusions Elevated levels of 30-130 nm EVs were found in plasma from ME/CFS patients and inter-cytokine correlations revealed unusual regulatory relationships among cytokines in the ME/CFS group that were different from the control group in both plasma and EVs. These disturbances in cytokine networks are further evidence of immune dysregulation in ME/CFS.

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“…The biogenesis of EXs and EMVs, and the triggers for their release from parent cells, are complex biological processes that eventually require the navigation of these vesicles through the extracellular matrix to their extracellular targets which may be near or distant (Barnes and Somerville 2020 [ 7 ]; Birgisdottir and Johansen 2020 [ 41 ]; BriteS 2020 [ 42 ]; Jadli et al, 2020 [ 43 ]). Protein interaction maps have indicated that EX and EMV biolipid boundary membranes have a tendency to interact with discrete extracellular “node” proteins involving surface ligands and delivery receptors, indicating an “ extracellular directional strategy ” for vesicular sorting and translocation over both short and long distances (Choi et al, 2015 [ 44 ]; Leidal and Debnath 2020 [ 45 ]).…”

Section: Extracellular Trafficking Of Ex and Emv Cargomentioning

confidence: 99%

Vesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells

Lukiw

Pogue²

2020

IJMS

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Exosomes (EXs) and extracellular microvesicles (EMVs) represent a diverse assortment of plasma membrane-derived nanovesicles, 30–1000 nm in diameter, released by all cell lineages of the central nervous system (CNS). They are examples of a very active and dynamic form of extracellular communication and the conveyance of biological information transfer essential to maintain homeostatic neurological functions and contain complex molecular cargoes representative of the cytoplasm of their cells of origin. These molecular cargoes include various mixtures of proteins, lipids, proteolipids, cytokines, chemokines, carbohydrates, microRNAs (miRNA) and messenger RNAs (mRNA) and other components, including end-stage neurotoxic and pathogenic metabolic products, such as amyloid beta (Aβ) peptides. Brain microglia, for example, respond to both acute CNS injuries and degenerative diseases with complex reactions via the induction of a pro-inflammatory phenotype, and secrete EXs and EMVs enriched in selective pathogenic microRNAs (miRNAs) such as miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155, and others that are known to promote neuro-inflammation, induce complement activation, disrupt innate–immune signaling and deregulate the expression of neuron-specific phosphoproteins involved in neurotropism and synaptic signaling. This communication will review our current understanding of the trafficking of miRNA-containing EXs and EMVs from astrocytes and “activated pro-inflammatory” microglia to target neurons in neurodegenerative diseases with an emphasis on Alzheimer’s disease wherever possible.

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Modulating Cytokine Production via Select Packaging and Secretion From Extracellular Vesicles

Cited by 61 publications

References 131 publications

Extracellular Vesicles in HTLV-1 Communication: The Story of an Invisible Messenger

Extracellular Vesicles in HTLV-1 Communication: The Story of an Invisible Messenger

Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study

Vesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells

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