Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-51062

Ribeiro, A; Wörnle, M; Anders, H J; Gröne, E F; Nitschko, H; Kurtschiev, P; Debiec, Hanna; Kretzler, M; Cohen, C D; Gröne, H J; Schlöndorff, D; Schmid, H (2012). Activation of innate immune defense mechanisms contributes to polyomavirus BK-associated nephropathy. Kidney International, 81(1):100-111.

[img]Published Version
PDF - Registered users only
450kB

View at publisher

Abstract

Polyomavirus-associated nephropathy (PVAN) is a significant
complication after kidney transplantation, often leading to
premature graft loss. In order to identify antiviral responses
of the renal tubular epithelium, we studied activation of the
viral DNA and the double-stranded RNA (dsRNA) sensors
Toll-like receptor 3 (TLR3) and retinoic acid inducible gene-I
(RIG-I) in allograft biopsy samples of patients with PVAN, and
in human collecting duct cells in culture after stimulation
by the dsRNA mimic polyriboinosinic:polyribocytidylic acid
(poly(I:C)), cytokines, or infection with BK virus. Double
staining using immunofluorescence for BK virus and TLR3
showed strong signals in epithelial cells of distal cortical
tubules and the collecting duct. In biopsies microdissected to
isolate tubulointerstitial lesions, TLR3 but not RIG-I mRNA
expression was found to be increased in PVAN. Collecting
duct cells in culture expressed TLR3 intracellularly, and
activation of TLR3 and RIG-I by poly(I:C) enhanced expression
of cytokine, chemokine, and IFN-b mRNA. This inflammatory
response could be specifically blocked by siRNA to TLR3.
Finally, infection of the collecting duct cells with BK virus
enhanced the expression of cytokines and chemokines. This
led to an efficient antiviral immune response with TLR3 and
RIG-I upregulation without activation of IL-1b or components
of the inflammasome pathway. Thus, PVAN activation of
innate immune defense mechanisms through TLR3 is involved
in the antiviral and anti-inflammatory response leading to the
expression of proinflammatory cytokines and chemokines.

Citations

5 citations in Web of Science®
7 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

2 downloads since deposited on 17 Nov 2011
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:17 Nov 2011 15:30
Last Modified:02 Dec 2013 00:34
Publisher:Nature Publishing Group
ISSN:0085-2538
Publisher DOI:10.1038/ki.2011.311
PubMed ID:21918500

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page