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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2008101067v1 20/9/1986    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Allam, R. Articles by Anders, H.-J. PubMed PubMed Citation Articles by Allam, R. Articles by Anders, H.-J.

Viral RNA and DNA Trigger Common Antiviral Responses in Mesangial Cells

Ramanjaneyulu Allam^*, Julia Lichtnekert^*, Anton G. Moll, Anela Taubitz^*, Volker Vielhauer^* and Hans-Joachim Anders^*

*Medizinische Poliklinik, University of Munich, Munich, Germany; and
Department of Nephrology, University of Zurich, Zurich, Switzerland

Correspondence: Dr. Hans-Joachim Anders, Medizinische Poliklinik, Universität München, Pettenkoferstrasse 8a, 80336 München, Germany. Phone: ++49-89- 218075855; Fax: ++49-89-218075860; E-mail: hjanders{at}med.uni-muenchen.de

Received for publication October 13, 2008. Accepted for publication May 15, 2009.

Extrarenal viral infections commonly trigger glomerulonephritis, usually in association with immune complex disease. The Ig component of immune complexes can activate glomerular cell Fc receptors, but whether complexed viral nucleic acids contribute to glomerular inflammation remains unknown. Because of the types of Toll-like receptors (Tlrs) expressed by glomerular mesangial cells, we hypothesized that viral single-stranded RNA and DNA would activate mesangial cells via Tlr-independent pathways and trigger overlapping antiviral immune responses. Consistent with this hypothesis, 5'-triphosphate RNA (3P-RNA) and non-CpG DNA activated murine primary glomerular mesangial cells to secrete Cxcl10 and Il-6 even in cells derived from mice deficient in the Tlr adaptor proteins Myd88 and Trif. Transcriptome analysis revealed that 3P-RNA and non-CpG-DNA triggered almost identical gene expression programs, especially the proinflammatory cytokine Il-6, several chemokines, and genes related to type I IFN. We observed similar findings in glomerular preparations after injecting 3P-RNA and non-CpG-DNA in vivo. These effects depended on the formation of complexes with cationic lipids, which enhanced nucleic acid uptake into the cytosol of mesangial cells. Small interfering RNA studies revealed that 3P-RNA recognition involves Rig-1, whereas non-CpG-DNA did not require Rig-1 or Dai to activate glomerular mesangial cells. We conclude that 3P-RNA and double-stranded DNA trigger a common, TLR-independent, antiviral response in glomerular mesangial cells, which may promote glomerulonephritis in the setting of viral infection.

This article has been cited by other articles:

				H. Hagele, R. Allam, R. D. Pawar, C. A. Reichel, F. Krombach, and H.-J. Anders Double-Stranded DNA Activates Glomerular Endothelial Cells and Enhances Albumin Permeability via a Toll-Like Receptor-Independent Cytosolic DNA Recognition Pathway Am. J. Pathol., November 1, 2009; 175(5): 1896 - 1904. [Abstract] [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673