Open AccessBacterial CpG-DNA Aggravates Immune Complex Glomerulonephritis
Author(s) -
HansJoachim Anders,
Bernhard Banas,
Yvonne Linde,
Lars Weller,
Clemens D. Cohen,
Matthias Kretzler,
Stefan Martin,
Volker Vielhauer,
Detlef Schlöndorff,
Hermann Josef Gröne
Publication year - 2003
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1097/01.asn.0000042169.23931.73
Subject(s) - tlr9 , chemokine , immune system , biology , tlr7 , glomerulonephritis , ccl5 , immunology , toll like receptor 9 , cpg oligodeoxynucleotide , cpg site , innate immune system , toll like receptor , kidney , endocrinology , gene expression , t cell , gene , dna methylation , biochemistry , il 2 receptor
. Immune complex glomerulonephritis (GN) often deteriorates during infection with viruses and bacteria that, in contrast to mammals, have DNA that contains many unmethylated CpG motifs. Balb/c mice with horse apoferritin-induced GN (HAF-GN) were treated with either saline, CpG-oligodeoxynucleotides (ODN), or control GpC-ODN. Only CpG-ODN exacerbated HAF-GN with an increase of glomerular macrophages, which was associated with massive albuminuria and increased renal MCP-1/CCL2, RANTES/CCL5, CCR1, CCR2, and CCR5 mRNA expression. CpG-ODN induced a Th1 response as indicated by serum anti-HAF IgG 2a titers, mesangial IgG 2a deposits, and splenocyte IFN-γ secretion. Messenger RNA for the CpG-DNA receptor Toll-like reeptor 9 (TLR9) was present in kidneys with HAF-GN but not in normal kidneys. The source of TLR9 mRNA in HAF-GN could be infiltrating macrophages or intrinsic renal cells, e.g. , mesangial cells; but, in vitro , only murine J774 macrophages expressed TLR9. In J774 cells, CpG-ODN induced the chemokines MCP-1/CCL2 and RANTES/CCL5 and the chemokine receptors CCR1 and CCR5. It is concluded that CpG-DNA can aggravate preexisting GN via a shift toward a Th1 response but also by a novel pathway involving TLR9-mediated chemokine and chemokine receptor expression by macrophages, which may contribute to the enhanced glomerular macrophage recruitment and activation. This mechanism may be relevant during infection-triggered exacerbation of human immune-complex GN and other immune-mediated diseases in general. E-mail: Detlef.Schloendorff@pk-i.med.uni-muenchen.de