Expression and regulation of Toll-like receptors in lupus-like immune complex glomerulonephritis of MRL-Fas(lpr) mice

Nephrol Dial Transplant. 2006 Nov;21(11):3062-73. doi: 10.1093/ndt/gfl336. Epub 2006 Sep 5.


Background: How microbial infections exacerbate immune complex glomerulonephritis remains speculative. Toll-like receptors (TLRs) may be involved in this phenomenon, because TLRs have potent immunostimulatory functions when exposed to selected pathogen-associated molecules.

Methods: We addressed this issue by characterizing the expression of TLR1-9 in MRLlpr/lpr mice that spontaneously develop immune complex glomerulonephritis as part of a systemic lupus-like autoimmune syndrome.

Results: Five-week-old healthy MRLlpr/lpr mice expressed TLR3 mRNA in kidneys at comparable levels as in the spleen, while all other TLRs were expressed at low levels in the kidney. In 20-week-old nephritic MRLlpr/lpr mice, renal mRNA levels had increased for TLR1-9. Renal TLR mRNA originated at least in part from glomeruli as evidenced by real-time RT-PCR from laser capture microdissected glomeruli. Immunostaining for TLR3, TLR7 and TLR9 revealed their expression by F4/80-positive infiltrating macrophages in 20-week-old nephritic MRLlpr/lpr mice. In addition, TLR3 localized to glomerular mesangial cells. Cultured mesangial cells expressed TLR1-4 and TLR6, while murine macrophages expressed TLR1-9. TNF-alpha and IFN-gamma induced TLR2, TLR3 and TLR6 mRNA in mesangial cells, while they down-regulated TLR1-9 mRNA in macrophages. Stimulation of both cell types with ligands for TLR1-4, TLR5, TLR7 and TLR9 induced IL-6 production consistent with their respective TLR expression patterns. TNF-alpha and IFN-gamma enhanced ligand-induced IL-6 production in both cell types irrespective of their modulatory effect on respective TLR mRNA levels.

Conclusion: Thus, cell-type-specific expression and regulation of TLRs may be involved in infection-associated exacerbation of immune complex glomerulonephritis of MRLlpr/lpr mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Immune Complex Diseases / immunology
  • Immune Complex Diseases / metabolism*
  • Immune Complex Diseases / pathology
  • Lupus Nephritis / immunology
  • Lupus Nephritis / metabolism*
  • Lupus Nephritis / pathology
  • Mice
  • Mice, Inbred MRL lpr
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • RNA, Messenger / biosynthesis
  • Toll-Like Receptors / biosynthesis*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism


  • RNA, Messenger
  • Toll-Like Receptors