Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells.
We have recently demonstrated that Epstein-Barr virus (EBV)-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate immunity in human primary monocyte-derived macrophages through toll-like receptor (TLR) 2 leading to NF-κB activation and the production of pro-inflammatory cy...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894549/?tool=EBI |
| _version_ | 1818721616442425344 |
|---|---|
| author | Maria Eugenia Ariza Pierre Rivailler Ronald Glaser Min Chen Marshall V Williams |
| author_facet | Maria Eugenia Ariza Pierre Rivailler Ronald Glaser Min Chen Marshall V Williams |
| author_sort | Maria Eugenia Ariza |
| collection | DOAJ |
| description | We have recently demonstrated that Epstein-Barr virus (EBV)-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate immunity in human primary monocyte-derived macrophages through toll-like receptor (TLR) 2 leading to NF-κB activation and the production of pro-inflammatory cytokines. Our previous depletion studies indicated that dendritic cells (DCs) may also be a target of the EBV-encoded dUTPase. However, the role of EBV-encoded dUTPase in DC activation/function and its potential contribution to the inflammatory cellular milieu characteristic of EBV-associated diseases remains poorly understood. In the present study, we demonstrate that EBV-encoded dUTPase significantly altered the expression of genes involved in oncogenesis, inflammation and viral defense mechanisms in human primary DCs by microarray analysis. Proteome array studies revealed that EBV-encoded dUTPase modulates DC immune responses by inducing the secretion of pro-inflammatory TH1/TH17 cytokines. More importantly, we demonstrate that EBV-encoded dUTPase is secreted in exosomes from chemically induced Raji cells at sufficient levels to induce NF-κB activation and cytokine secretion in primary DCs and peripheral blood mononuclear cells (PBMCs). Interestingly, the production of pro-inflammatory cytokines in DCs and PBMCs was TLR2-dependent. Together these findings suggest that the EBV-encoded dUTPase may act as an intercellular signaling molecule capable of modulating the cellular microenvironment and thus, it may be important in the pathophysiology of EBV related diseases. |
| first_indexed | 2024-12-17T20:41:34Z |
| format | Article |
| id | doaj.art-a783f41627084735b007eec3155aaa18 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T20:41:34Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a783f41627084735b007eec3155aaa182022-12-21T21:33:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6982710.1371/journal.pone.0069827Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells.Maria Eugenia ArizaPierre RivaillerRonald GlaserMin ChenMarshall V WilliamsWe have recently demonstrated that Epstein-Barr virus (EBV)-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate immunity in human primary monocyte-derived macrophages through toll-like receptor (TLR) 2 leading to NF-κB activation and the production of pro-inflammatory cytokines. Our previous depletion studies indicated that dendritic cells (DCs) may also be a target of the EBV-encoded dUTPase. However, the role of EBV-encoded dUTPase in DC activation/function and its potential contribution to the inflammatory cellular milieu characteristic of EBV-associated diseases remains poorly understood. In the present study, we demonstrate that EBV-encoded dUTPase significantly altered the expression of genes involved in oncogenesis, inflammation and viral defense mechanisms in human primary DCs by microarray analysis. Proteome array studies revealed that EBV-encoded dUTPase modulates DC immune responses by inducing the secretion of pro-inflammatory TH1/TH17 cytokines. More importantly, we demonstrate that EBV-encoded dUTPase is secreted in exosomes from chemically induced Raji cells at sufficient levels to induce NF-κB activation and cytokine secretion in primary DCs and peripheral blood mononuclear cells (PBMCs). Interestingly, the production of pro-inflammatory cytokines in DCs and PBMCs was TLR2-dependent. Together these findings suggest that the EBV-encoded dUTPase may act as an intercellular signaling molecule capable of modulating the cellular microenvironment and thus, it may be important in the pathophysiology of EBV related diseases.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894549/?tool=EBI |
| spellingShingle | Maria Eugenia Ariza Pierre Rivailler Ronald Glaser Min Chen Marshall V Williams Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. PLoS ONE |
| title | Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. |
| title_full | Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. |
| title_fullStr | Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. |
| title_full_unstemmed | Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. |
| title_short | Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. |
| title_sort | epstein barr virus encoded dutpase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894549/?tool=EBI |
| work_keys_str_mv | AT mariaeugeniaariza epsteinbarrvirusencodeddutpasecontainingexosomesmodulateinnateandadaptiveimmuneresponsesinhumandendriticcellsandperipheralbloodmononuclearcells AT pierrerivailler epsteinbarrvirusencodeddutpasecontainingexosomesmodulateinnateandadaptiveimmuneresponsesinhumandendriticcellsandperipheralbloodmononuclearcells AT ronaldglaser epsteinbarrvirusencodeddutpasecontainingexosomesmodulateinnateandadaptiveimmuneresponsesinhumandendriticcellsandperipheralbloodmononuclearcells AT minchen epsteinbarrvirusencodeddutpasecontainingexosomesmodulateinnateandadaptiveimmuneresponsesinhumandendriticcellsandperipheralbloodmononuclearcells AT marshallvwilliams epsteinbarrvirusencodeddutpasecontainingexosomesmodulateinnateandadaptiveimmuneresponsesinhumandendriticcellsandperipheralbloodmononuclearcells |