COVID-19 plasma exosomes promote pro-inflammatory immune responses in peripheral blood mononuclear cells Article Swipe
Lechuang Chen
,
Rui Chen
,
Min Yao
,
Zhimin Feng
,
Guoxiang Yuan
,
Fengchun Ye
,
Kien Nguyen
,
Jonathan Karn
,
Grace A. McComsey
,
Thomas M. McIntyre
,
Ge Jin
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1950248/v2
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1950248/v2
Elevated serum cytokine production in COVID-19 patients is associated with disease progression and severity. However, the stimulus that initiates cytokine production in patients remains to be fully revealed. Virus-infected cells can release virus-associated exosomes, extracellular vesicles (EVs) of endocytic origin, into the blood to deliver viral cargoes able to regulate immune responses. Here, we report that plasma exosomes from COVID-19 patients contain SARS-CoV-2 RNA. COVID-19 plasma exosomes stimulated robust production of interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and other inflammatory cytokines and chemokines in human peripheral mononuclear cells (PBMCs). Exosome depletion abolished these stimulated responses. COVID-19 plasma exosomes induced proinflammatoryresponses in CD4+ T cells, CD8+ T cells, and CD14+monocytes but not significantly in regulatory T cells, Th17 T cells, or memory T cells. COVID-19 plasma exosomes carry viral double-stranded RNA (dsRNA) intermediates, protect the dsRNA cargo from RNase, and deliver the dsRNA to recipient cells. COVID-19 plasma exosomes significantly increase the expression of endosomal toll-like receptor 3 (TLR3), TLR7, TLR8, and TLR9 in peripheral T cells and monocytes. Inhibition of TLR3 by a specific pharmacological inhibitor considerably reduced the production of cytokines and chemokines in CD4+ and CD8+ T cells but not in CD14+monocytes, highlighting divergent signaling pathways of immune cells in response to COVID-19 plasma exosomes. Our results indicate a novel model of crosstalk between SARS-CoV-2 infection and immune responses able to contribute to elevated cytokine production associated with COVID-19 progression, severity, and long-haul symptoms.
Related Topics
Concepts
Immune system
Microvesicles
Chemokine
CD14
Biology
Cytokine
TLR3
Immunology
Peripheral blood mononuclear cell
Inflammation
Tumor necrosis factor alpha
Toll-like receptor
Innate immune system
microRNA
Gene
Biochemistry
In vitro
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-1950248/v2
- https://www.researchsquare.com/article/rs-1950248/latest.pdf
- OA Status
- green
- References
- 64
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4296385055
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4296385055Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-1950248/v2Digital Object Identifier
- Title
-
COVID-19 plasma exosomes promote pro-inflammatory immune responses in peripheral blood mononuclear cellsWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-09-19Full publication date if available
- Authors
-
Lechuang Chen, Rui Chen, Min Yao, Zhimin Feng, Guoxiang Yuan, Fengchun Ye, Kien Nguyen, Jonathan Karn, Grace A. McComsey, Thomas M. McIntyre, Ge JinList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-1950248/v2Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-1950248/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-1950248/latest.pdfDirect OA link when available
- Concepts
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Immune system, Microvesicles, Chemokine, CD14, Biology, Cytokine, TLR3, Immunology, Peripheral blood mononuclear cell, Inflammation, Tumor necrosis factor alpha, Toll-like receptor, Innate immune system, microRNA, Gene, Biochemistry, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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64Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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