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TLR2 stimulation of intrinsic renal cells in the induction of immune-mediated glomerulonephritis.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2006 Aug 01; Vol. 177 (3), pp. 1925-31. - Publication Year :
- 2006
-
Abstract
- Infection may exacerbate organ-specific autoimmune disease such as glomerulonephritis. This may occur in the absence of a measurable effect on the adaptive immune response, and the mechanisms responsible are not fully understood. To investigate this, we have studied the effect of TLR2 ligation by the synthetic ligand Pam(3)CysSK(4) on the development of glomerulonephritis in mice. We demonstrated that glomerular inflammation induced by passive administration of nephrotoxic Ab does not occur in the absence of TLR2 stimulation, with a strong synergy when Ab deposition and TLR2 stimulation occur together. Parameters of glomerular inflammation were neutrophil influx, thrombosis, and albuminuria. To investigate the relative contribution of TLR2 on bone marrow-derived cells and intrinsic renal cells, we constructed bone marrow chimeras. Nephrotoxic Ab and TLR2 ligation caused a neutrophil influx in both types of chimera above [corrected] that seen in sham chimeras totally TLR2 deficient [corrected] Albuminuria was seen in both types of chimera above that seen in sham chimeras that were totally TLR2 deficient. This was greater in chimeras with TLR2 present on bone marrow-derived cells. To find a potential mechanism by which intrinsic renal cells may contribute toward disease exacerbation, mesangial cells were studied and shown to express TLR2 and MyD88. Wild-type but not TLR2-deficient mesangial cells produced CXC chemokines in response to stimulation with Pam(3)CysSK(4). These results demonstrate that TLR2 stimulation on both bone marrow-derived and resident tissue cells plays a role in amplifying the inflammatory effects of Ab deposition in the glomerulus.
- Subjects :
- Adaptor Proteins, Signal Transducing biosynthesis
Albuminuria immunology
Albuminuria metabolism
Albuminuria pathology
Animals
Bone Marrow Cells immunology
Bone Marrow Cells metabolism
Cell Movement immunology
Chemokines, CXC biosynthesis
Endotoxins administration & dosage
Endotoxins blood
Glomerular Mesangium immunology
Glomerular Mesangium metabolism
Glomerulonephritis genetics
Glomerulonephritis metabolism
Immunoglobulin G metabolism
Injections, Intravenous
Kidney Glomerulus metabolism
Leukocyte Count
Lipopeptides
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
Neutrophils pathology
Peptides administration & dosage
Severity of Illness Index
Toll-Like Receptor 2 antagonists & inhibitors
Toll-Like Receptor 2 biosynthesis
Toll-Like Receptor 2 deficiency
Glomerulonephritis immunology
Glomerulonephritis pathology
Kidney Glomerulus immunology
Kidney Glomerulus pathology
Toll-Like Receptor 2 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 177
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 16849506
- Full Text :
- https://doi.org/10.4049/jimmunol.177.3.1925