Mired in the glomeruli: witnessing live neutrophil recruitment in the kidney

Abstract

Inflammation of the kidney is a key contributor to proliferative glomerulonephritis, and kidney damage during glomerulonephritis can lead to renal failure. The immune response associated with glomerulonephritis episodes is a major determinant of patient outcomes, and understanding this response is paramount for effective therapeutic treatment. Neutrophils are the first responders to sites of infection or tissue injury and are a significant cellular infiltrate during proliferative glomerulonephritis. This immune cell was initially recognized as a “blunt” nonspecific effector cell that was recruited to kill pathogens and then die quickly. However, recent studies have shown that the behavior and function of neutrophils are substantially more complex. Neutrophil recruitment to inflammatory sites must be carefully regulated so that these potent cells accurately arrive at tissue sites and perform their functions without nonspecific injury to other locations. As the kidney contains unique microvasculature befitting their specialized role in blood filtration, the recruitment of neutrophils in the renal environment differs from other organs. This Mini-Review will describe how advances in live-animal (intravital) imaging led to the discovery of novel recruitment pathways in the kidney, particularly in the glomeruli, and highlight these differences to canonical neutrophil recruitment. In addition, molecular engagement of surface molecules that lead to intracellular signaling, which is followed by neutrophil capture in the glomeruli, is also briefly discussed. Finally, the contribution of other immune cells in renal neutrophil recruitment, the fate of the emigrated neutrophils after inflammation, and the relevance of mouse models compared with human glomerulonephritides will also be explored.