RGD Reference Report - The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. - Rat Genome Database

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The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.

Authors: Hovius, JW  Bijlsma, MF  Van der Windt, GJ  Wiersinga, WJ  Boukens, BJ  Coumou, J  Oei, A  De Beer, R  De Vos, AF  Van 't Veer, C  Van Dam, AP  Wang, P  Fikrig, E  Levi, MM  Roelofs, JJ  Van der Poll, T 
Citation: Hovius JW, etal., PLoS Pathog. 2009 May;5(5):e1000447. Epub 2009 May 22.
RGD ID: 6483813
Pubmed: PMID:19461880   (View Abstract at PubMed)
PMCID: PMC2678258   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.ppat.1000447   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PLAURHumanLyme disease  ISOPlaur (Mus musculus) RGD 
PLAURHumanLyme disease  IEP mRNA:increased expression:skinRGD 
PlaurRatLyme disease  ISOPlaur (Mus musculus) RGD 
PlaurRatLyme disease  ISOPLAUR (Homo sapiens)mRNA:increased expression:skinRGD 
PlaurMouseLyme disease  ISOPLAUR (Homo sapiens)mRNA:increased expression:skinRGD 
PlaurMouseLyme disease  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Plaur  (plasminogen activator, urokinase receptor)

Genes (Mus musculus)
Plaur  (plasminogen activator, urokinase receptor)

Genes (Homo sapiens)
PLAUR  (plasminogen activator, urokinase receptor)


Additional Information