Macrophage polarization in innate immune responses contributing to pathogenesis of chronic kidney disease

Abstract

Chronic kidney disease (CKD) is characterized by inflammation, injury and fibrosis. Dysregulated innate immune responses mediated by macrophages play critical roles in progressive renal injury. The differentiation and polarization of macrophages into pro-inflammatory 'M1' and anti-inflammatory 'M2' states represent the two extreme maturation programs of macrophages during tissue injury. However, the effects of macrophage polarization on the pathogenesis of CKD are not fully understood. In this review, we discuss the innate immune mechanisms underlying macrophage polarization and the role of macrophage polarization in the initiation, progression, resolution and recurrence of CKD. Macrophage activation and polarization are initiated through recognition of conserved endogenous and exogenous molecular motifs by pattern recognition receptors, chiefly, Toll-like receptors (TLRs), which are located on the cell surface and in endosomes, and NLR inflammasomes, which are positioned in the cytosol. Recent data suggest that genetic variants of the innate immune molecule apolipoprotein L1 (APOL1) that are associated with increased CKD prevalence in people of African descent, mediate an atypical M1 macrophage polarization. Manipulation of macrophage polarization may offer novel strategies to address dysregulated immunometabolism and may provide a complementary approach along with current podocentric treatment for glomerular diseases.