CD11b is protective in complement-mediated immune complex glomerulonephritis

In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex-mediated glomerulonephritis in CfH -/- mice chimeric for wild-type, CfH -/-, CD11b -/-, or FcRγ -/- bone marrow stem cells. Glomerulonephritis was worse in CD11b -/- chimeras compared with all others, whereas disease in FcRγ -/- and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b -/- chimeras had significantly more M1 macrophages and CD4 + T cells. The renal dendritic cell populations originating from bone marrow-derived CD11c + cells were similar in all experimental groups. CD11b + cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b -/- chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex-mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4 + T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney.