Exosomes from COVID-19 patients carry tenascin-C and fibrinogen-β in triggering inflammatory signals in distant organ cells

Abstract

SARS-CoV-2 infection causes cytokine storm and overshoot immunity in humans; however, it remains to be determined whether genetic material of SARS-CoV-2 and/or virus induced soluble mediators from lung epithelial cells as natural host are carried out by macrophages or other vehicles at distant organs causing tissue damage. We speculated that exosomes as extracellular vesicles are secreted from SARS-CoV-2 infected cells may transport messages to other cells of distant organs leading to pathogenic consequences. For this, we took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and SARS-CoV-2 infected patients. Our results revealed that tenascin-C (TNC) and fibrinogen-β (FGB) are highly abundant in exosomes from SARS-CoV-2 infected patient's plasma as compared to that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via NF-kB pathway, we examined the status of TNF-a, IL-6 and CCL5 expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase when compared with that from healthy subjects. Together, our results demonstrated that soluble mediators, like TNC and FGB, are transported through plasma exosomes in SARS-CoV-2 infected patients and trigger pro-inflammatory cytokine expression in cells of distant organs in COVID-19 patients.

Diverse Effects of Exosomes on COVID-19: A Perspective of Progress From Transmission to Therapeutic Developments

“…Plasma exosomes from COVID-19 infected patients contains high level of tenascin-C (TNC) and fibrinogen-β (FGB) compared to that of healthy normal controls. Both TNC and FGB stimulate pro-inflammatory cytokines via NF-κB pathway ( 216 ). Exosomes contains non-coding RNAs play a crucial role in virus mediated disease progression.…”

“…The presence of TNC and FGB in SARS-CoV-2 infected patient exosomes may be a mechanism for cytokine storm resulting in micro-thrombosis in some patients and TNC and/or FGB can be used as the potential prognostic markers for COVID-19 patients. TNC and FGB-enriched exosomes from COVID-19 plasma and may be correlated for the first time with pathogenesis ( 216 ) Fujita et al. reported that antiviral response-related EV proteins, coagulation-related markers, and liver damage-related exRNAs serving as potential early predictive biomarkers for COVID-19 severity ( 217 ).…”

Extracellular Vesicles: An Emerging Mechanism Governing the Secretion and Biological Roles of Tenascin-C

“…Exosomes have also recently emerged as efficient platforms for immunomodulation in the tumor microenvironment and other tissue contexts (131,215); it is likely that the prominent roles TnC has as a regulator of immune cell function (see first section) are exerted at least in part through exosomes. Interestingly, exosomes released by SARS-CoV2-infected cells are significantly enriched in TnC and could promote the propagation of inflammation to distant sites (216). Serum TnC levels have been explored as diagnostic/prognostic markers in different pathologies (24), but whether all circulating TnC is exclusively trafficked through EVs is yet to be determined.…”

Integrated Analysis of microRNAs and Metabolomics in Rat’s Serum Reveals Multi-action Modes of Qingfei Paidu Decoction for COVID-19 Treatment

“…Involving regulation of immunity [114,115], in ammatory cytokines [114,[116][117][118][119][120], pulmonary brosis [121], and virus infection, e.g., SARS-CoV-2, H1N1 [115][116][117][119][120][121][122][123][124] Cytokine-cytokine receptor interaction…”