Both classical and non-classical monocytes patrol glomerular capillaries and promote acute glomerular inflammation.

Abstract

Monocyte patrolling of the vasculature has been ascribed primarily to the non-classical monocyte subset. However, a recent study of the glomerular microvasculature provided evidence that both classical and non-classical monocytes can undergo periods of intravascular retention and migration. Despite this, whether these subsets contribute differentially to acute glomerular inflammation is unknown. This study used glomerular multiphoton intravital microscopy to investigate the capacity of classical and non-classical monocytes to patrol the glomerular microvasculature and promote acute, neutrophil-dependent glomerular inflammation. In imaging experiments in monocyte reporter Cx3cr1gfp/+ mice, co-staining with anti-Ly6B or anti-Ly6C revealed that both non-classical (CX3CR1-GFP+) and classical (CX3CR1-GFP+ & Ly6B+ or Ly6C+) monocytes undergo prolonged (> 10 minutes) retention and migration in the glomerular microvasculature. Induction of acute glomerulonephritis caused increases in these behaviors for classical but not non-classical monocytes. Using non-classical monocyte-deficient Csf1rCreNr4a1fl/fl mice, or anti-CCR2 to deplete classical monocytes, removal of either subset reduced neutrophil retention and activation in acutely-inflamed glomeruli, while depletion of both subsets, via anti-CCR2 treatment of Csf1rCreNr4a1fl/fl mice, led to further reductions in neutrophil activity. In contrast, in a model of CD4+ T cell-dependent glomerulonephritis, depletion of either monocyte subset failed to alter neutrophil responses. These findings indicate that both classical and non-classical monocytes patrol the glomerular microvasculature and can promote neutrophil responses in acutely inflamed glomeruli.Copyright © 2024. Published by Elsevier Inc.