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

Kidney Int. 2005 Dec;68(6):2582-7. doi: 10.1111/j.1523-1755.2005.00729.x.


Background: The molecular mechanisms of pathogen recognition that initiate infective pyelonephritis are poorly understood. Toll-like receptor-4 (TLR4) mutant mice infected with uropathogenic Escherichia coli lack renal CXCL2 mRNA expression, subsequent neutrophil recruitment, and renal abscess formation.

Methods: We 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.

Results: Both chimera either expressing mutant tlr4 in intrinsic renal cells and wild-type tlr4 in bone marrow-derived cells or vice versa showed an impaired response to uropathogenic E. coli infection in terms of leukocyturia and renal abscess formation when compared to tlr4 wild-type mice with congenic bone marrow transplants.

Conclusion: These 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 uropathogenic E. coli infection by initiating chemokine-driven renal neutrophil recruitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Transplantation
  • Cells, Cultured
  • Chemokine CXCL2
  • Chemokines / genetics
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / immunology
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / metabolism
  • Kidney Tubules / cytology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C3H
  • Mice, Mutant Strains
  • Mutant Chimeric Proteins / genetics
  • Mutant Chimeric Proteins / metabolism
  • Neutrophils / cytology*
  • Neutrophils / immunology
  • Pyelonephritis / immunology*
  • Pyelonephritis / metabolism*
  • Pyelonephritis / microbiology
  • RNA, Messenger / analysis
  • Signal Transduction / immunology
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*


  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • Lipopolysaccharides
  • Mutant Chimeric Proteins
  • RNA, Messenger
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4