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Updated: Jul 14, 2026

Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Coactivation of Toll-like receptor-3 and -7 in immune complex glomerulonephritis
Prashant S Patole1, Rahul D Pawar, Julia Lichtnekert
1Medical Policlinic, Ludwig-Maximilians-University Munich, Pettenkoferstr. 8a, 80336 Munich, Germany.
Abstract:
The molecular mechanisms of viral infection-induced glomerulonephritis are poorly understood. Toll-like receptor (TLR)-3 and TLR7 recognize viral RNA and their exposure to TLR3 or TLR7 can trigger the exacerbation of established immune complex disease in MRLlpr mice. Because coactivation of TLR3 and TLR7 was shown to synergistically activate dendritic cells in vitro, we hypothesized that simultaneous ligation of TLR3 and TLR7 would elicit additive effects on the exacerbation of glomerulonephritis in MRLlpr mice. Saline, 50 microg pI:C RNA, 25 microg of the TLR7 agonist imiquimod, or a combination of both were injected every other day to MRLlpr mice from week 16-18 of age. Coinjection of pI:C RNA and imiquimod had no synergistic effect on serum levels of IL-6 and IL12p70, dsDNA autoantibody levels, and glomerulonephritis. This was consistent with a lack of synergistic effects on cytokine release of TNF- and IFNgamma-prestimulated monocytes in vitro. Furthermore, in glomerular mesangial cells a synergistic effect of pI:C RNA and imiquimod was generally absent due to the lack of TLR7 expression. We conclude that a number of mechanisms protect the host from additive effects of TLR3-TLR7 coactivation on renal pathology in vivo.
Insights
Simultaneous activation of Toll-like receptor (TLR)-3 and TLR7 did not worsen glomerulonephritis in mice. This suggests mechanisms protect against additive TLR3-TLR7 coactivation effects on kidney disease.
Area of Science:
- Immunology
- Nephrology
- Molecular Biology
Background:
- Viral infections can trigger glomerulonephritis, a kidney inflammation.
- Toll-like receptors (TLRs) like TLR3 and TLR7 recognize viral RNA and can worsen kidney disease.
- Previous studies suggested TLR3 and TLR7 coactivation might synergistically impact immune responses.
Purpose of the Study:
- To investigate if simultaneous TLR3 and TLR7 activation exacerbates glomerulonephritis in MRLlpr mice.
- To determine if coactivation leads to additive effects on immune markers and kidney pathology.
Main Methods:
- MRLlpr mice were treated with saline, poly(I:C) (TLR3 agonist), imiquimod (TLR7 agonist), or a combination.
- Treatments were administered bi-daily from week 16 to 18 of age.
- Serum levels of cytokines (IL-6, IL12p70), anti-dsDNA antibodies, and glomerulonephritis severity were assessed.
Main Results:
- Combined TLR3 and TLR7 agonist treatment did not show synergistic effects on serum cytokines, autoantibodies, or glomerulonephritis.
- In vitro studies showed no synergistic cytokine release from monocytes.
- Glomerular mesangial cells lacked TLR7 expression, preventing synergistic responses.
Conclusions:
- Coactivation of TLR3 and TLR7 does not have additive effects on exacerbating glomerulonephritis in MRLlpr mice.
- Mechanisms exist that protect against detrimental additive effects of TLR3-TLR7 coactivation on renal pathology.
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