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


CONCLUSIONS
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.
Patole
Prashant S
PS
Medizinische Poliklinik-Innenstadt, University of Munich, Munich, Germany.
Schubert
Sören
S
Hildinger
Kirsten
K
Khandoga
Sascha
S
Khandoga
Andrej
A
Segerer
Stephan
S
Henger
Anna
A
Kretzler
Matthias
M
Werner
Melanie
M
Krombach
Fritz
F
Schlöndorff
Detlef
D
Anders
Hans-Joachim
HJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D050506:Mutant Chimeric Proteins / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D011704:Pyelonephritis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; D050506:Mutant Chimeric Proteins; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4