The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.
The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-05-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC2678258?pdf=render |
| _version_ | 1818301297884921856 |
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| author | Joppe W R Hovius Maarten F Bijlsma Gerritje J W van der Windt W Joost Wiersinga Bastiaan J D Boukens Jeroen Coumou Anneke Oei Regina de Beer Alex F de Vos Cornelis van 't Veer Alje P van Dam Penghua Wang Erol Fikrig Marcel M Levi Joris J T H Roelofs Tom van der Poll |
| author_facet | Joppe W R Hovius Maarten F Bijlsma Gerritje J W van der Windt W Joost Wiersinga Bastiaan J D Boukens Jeroen Coumou Anneke Oei Regina de Beer Alex F de Vos Cornelis van 't Veer Alje P van Dam Penghua Wang Erol Fikrig Marcel M Levi Joris J T H Roelofs Tom van der Poll |
| author_sort | Joppe W R Hovius |
| collection | DOAJ |
| description | The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here demonstrate that uPAR is upregulated on murine and human leukocytes upon exposure to B. burgdorferi both in vitro as well as in vivo. Notably, B. burgdorferi-inoculated C57BL/6 uPAR knock-out mice harbored significantly higher Borrelia numbers compared to WT controls. This was associated with impaired phagocytotic capacity of B. burgdorferi by uPAR knock-out leukocytes in vitro. B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity) and PAI-1 (high fibrinolytic activity) knock-out mice compared to WT controls. Strikingly, in uPAR knock-out mice partially backcrossed to a B. burgdorferi susceptible C3H/HeN background, higher B. burgdorferi numbers were associated with more severe carditis and increased local TLR2 and IL-1beta mRNA expression. In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system. |
| first_indexed | 2024-12-13T05:20:47Z |
| format | Article |
| id | doaj.art-6f9fcfb5f14841adaa06c80d9d122a46 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T05:20:47Z |
| publishDate | 2009-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-6f9fcfb5f14841adaa06c80d9d122a462022-12-21T23:58:19ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742009-05-0155e100044710.1371/journal.ppat.1000447The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.Joppe W R HoviusMaarten F BijlsmaGerritje J W van der WindtW Joost WiersingaBastiaan J D BoukensJeroen CoumouAnneke OeiRegina de BeerAlex F de VosCornelis van 't VeerAlje P van DamPenghua WangErol FikrigMarcel M LeviJoris J T H RoelofsTom van der PollThe causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here demonstrate that uPAR is upregulated on murine and human leukocytes upon exposure to B. burgdorferi both in vitro as well as in vivo. Notably, B. burgdorferi-inoculated C57BL/6 uPAR knock-out mice harbored significantly higher Borrelia numbers compared to WT controls. This was associated with impaired phagocytotic capacity of B. burgdorferi by uPAR knock-out leukocytes in vitro. B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity) and PAI-1 (high fibrinolytic activity) knock-out mice compared to WT controls. Strikingly, in uPAR knock-out mice partially backcrossed to a B. burgdorferi susceptible C3H/HeN background, higher B. burgdorferi numbers were associated with more severe carditis and increased local TLR2 and IL-1beta mRNA expression. In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system.http://europepmc.org/articles/PMC2678258?pdf=render |
| spellingShingle | Joppe W R Hovius Maarten F Bijlsma Gerritje J W van der Windt W Joost Wiersinga Bastiaan J D Boukens Jeroen Coumou Anneke Oei Regina de Beer Alex F de Vos Cornelis van 't Veer Alje P van Dam Penghua Wang Erol Fikrig Marcel M Levi Joris J T H Roelofs Tom van der Poll The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. PLoS Pathogens |
| title | The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. |
| title_full | The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. |
| title_fullStr | The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. |
| title_full_unstemmed | The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. |
| title_short | The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. |
| title_sort | urokinase receptor upar facilitates clearance of borrelia burgdorferi |
| url | http://europepmc.org/articles/PMC2678258?pdf=render |
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