Circulating extracellular vesicles as new inflammation marker in HIV infection

Abstract

Background: Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients. Methods: We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31+/CD41a−/CD45−, EMVs), extracellular vesicles stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis. Results: Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients. Conclusion: These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.

Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword

“…Platelet activation is indeed a recurrent parameter observed in platelets from people living with HIV, or upon the in vitro infection of healthy platelets. In addition, the alteration of platelets’ mitochondrial inflammatory response [ 220 ], sometimes with platelet exhaustion [ 52 , 221 ], and the increased release of inflammatory microparticles [ 222 ] make platelets central contributors to the HIV-1-related chronic inflammation that increases the risk of cardiovascular complications.…”

Phenotypic and Proteomic Analysis Identifies Hallmarks of Blood Circulating Extracellular Vesicles in NSCLC Responders to Immune Checkpoint Inhibitors

“…Extracellular vesicle concentrations were obtained by volumetric count, using an instrument (BD FACSVerse™ flow cytometer) equipped by the volumetric count device. Such a function is largely used in flow cytometry to assess event counts [22,23].…”

What Function Do Platelets Play in Inflammation and Bacterial and Viral Infections?

“…This causes coronary occlusion and may lead to atheromatous plaque rupture and inflammation. The involvement of platelets was also recorded in myocarditis caused by the infections with entero-, adeno- and herpesviruses, parvovirus B19, HIV and influenza virus, as they enhance the immune status and inflammation if activated by these infectious agents, acting together with the cells of the blood immune system ( 83 , 113 ). Moreover, HIV infection has been shown to increase the amount of EV of platelets and their products, including the activity of IFNɣ and IL-1α, which also increases inflammation ( 113 ).…”

“…The involvement of platelets was also recorded in myocarditis caused by the infections with entero-, adeno- and herpesviruses, parvovirus B19, HIV and influenza virus, as they enhance the immune status and inflammation if activated by these infectious agents, acting together with the cells of the blood immune system ( 83 , 113 ). Moreover, HIV infection has been shown to increase the amount of EV of platelets and their products, including the activity of IFNɣ and IL-1α, which also increases inflammation ( 113 ). The involvement of platelets was also found in patients with asthma, pneumonia, atherosclerosis and vascular diseases, as well as inflammation of the mouth, large intestine and kidneys, which are conditions caused, among others, by the interaction of these cells with monocytes, which leads to an increase in the platelet/monocyte complexes and increased secretion of cytokines activating the immune state and inflammation ( 6 , 15 , 33 – 35 , 40 , 66 , 76 , 78 , 98 , 102 , 114 , 115 ).…”