Basic Immunology and PathologyToll-Like Receptor-7 Modulates Immune Complex GlomerulonephritisPawar, Rahul D.; Patole, Prashant S.; Zecher, Daniel; Segerer, Stephan; Kretzler, Matthias; Schlo[Combining Diaeresis]ndorff, Detlef; Anders, Hans-Joachim Author Information Nephrological Center, Medical Policlinic, University of Munich, Munich, Germany Address correspondence to: Dr. Hans-Joachim Anders, Medizinische Poliklinik, Klinikum der Universita[Combining Diaeresis]t–Innenstadt, Pettenkoferstrasse 8a, 80336 Munich, Germany. Phone: +49-89-2180-75846; Fax: +49-89-2180-75860; [email protected] Accepted September 28, 2005 Received July 13, 2005 Journal of the American Society of Nephrology 17(1):p 141-149, January 2006. | DOI: 10.1681/ASN.2005070714 Buy Metrics Abstract Viral infections may trigger immune complex glomerulonephritis via Toll-like receptors (TLR), as certain TLR trigger immunity upon recognition of viral nucleic acids. On the basis of previous findings regarding viral double-stranded RNA and TLR3 in experimental lupus erythematosus, a similar role for TLR7 that recognizes viral single-stranded RNA was hypothesized. Immunostaining of kidney sections of nephritic MRLlpr/lpr mice revealed TLR7 expression in infiltrating ER-HR3–positive macrophages and few CD11c-positive dendritic cells but not in glomerular mesangial cells as observed for TLR3. This finding was consistent with the distribution pattern of intravenously injected single-stranded RNA in nephritic MRLlpr/lpr mice. TLR7 ligation activated monocytes and dendritic cells, both isolated from MRLlpr/lpr mice, to secrete IFN-α, IL-12p70, IL-6, and CCL2. In vivo, a single injection of the TLR7 ligand imiquimod increased serum levels of IL-12p70, IFN-α, and IL-6. A course of 25 μg of imiquimod given every other day from week 16 to 18 of age aggravated lupus nephritis in MRLlpr/lpr mice. This was associated with increased glomerular immune complex deposits as well as interstitial expression of CCL2 in imiquimod-treated MRLlpr/lpr mice. Different types of viral nucleic acids seem to modulate systemic autoimmunity through specific interactions with their respective TLR. Different TLR expression profiles on immune cell subsets and nonimmune parenchymal cell types determine the molecular mechanisms involved in viral infection–associated exacerbation of lupus nephritis and possibly other types of immune complex glomerulonephritis. Copyright © 2006 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.