Toll-like receptor-4: Renal cells and bone marrow cells signal for neutrophil recruitment during pyelonephritis

Toll-like receptor-4: Renal cells and bone marrow cells signal for neutrophil recruitment during pyelonephritis.BackgroundThe molecular mechanisms of pathogen recognition that initiate infective pyelonephritis are poorly understood. Toll-like receptor-4 (TLR4) mutant mice infected with uropathogenicEscherichia coli lack renal CXCL2 mRNA expression, subsequent neutrophil recruitment, and renal abscess formation.MethodsWe used a bone marrow transplant approach in order to investigate the contribution of TLR4 in intrinsic renal cells or bone-marrow-derived immune cells to neutrophil recruitment during infective pyelonephritis.ResultsBoth chimera either expressing mutanttlr4 in intrinsic renal cells and wild-typetlr4 in bone marrow-derived cells or vice versa showed an impaired response to uropathogenicE. coli infection in terms of leukocyturia and renal abscess formation when compared totlr4 wild-type mice with congenic bone marrow transplants.ConclusionThese data suggest that TLR4 is required on both intrinsic renal cells (e.g., tubular epithelial cells) and bone marrow-derived immune cells for the control of ascending uropathogenicE. coli infection by initiating chemokine-driven renal neutrophil recruitment.