title: Cathelicidin augments epithelial receptivity and pathogenesis in experimental Escherichia coli cystitis.
abstract: BACKGROUND
  Cathelicidin is a proposed defender against infection of the urinary tract via its antimicrobial properties, but its activity has not been delineated in a dedicated cystitis model.
  
  
  METHODS
  Female C57Bl/6 mice, wild type or deficient in cathelin-related antimicrobial peptide (CRAMP; an ortholog of the sole human cathelicidin, LL-37), were infected transurethrally with the cystitis-derived uropathogenic Escherichia coli (UPEC) strain UTI89. Infection course was evaluated by bladder titers, intracellular bacterial community quantification, and histological analysis. Immune responses and resolution were characterized through cytokine profiling, microscopy, and quantitation of epithelial recovery from exfoliation.
  
  
  RESULTS
  CRAMP-deficient mice exhibited significantly lower bladder bacterial loads and fewer intracellular bacterial communities during acute cystitis. Although differences in bacterial titers were evident as early as 1 hour after infection, CRAMP-deficient mice showed no baseline alterations in immune activation, uroepithelial structure, apical expression of uroplakins (which serve as bacterial receptors), or intracellular bacterial growth rate. CRAMP-deficient hosts demonstrated less intense cytokine responses, diminished neutrophil infiltration, and accelerated uroepithelial recovery.
  
  
  CONCLUSIONS
  Mice lacking the antimicrobial peptide cathelicidin experienced less severe infection than wild-type mice in a well-established model of cystitis. Although CRAMP exhibits in vitro antibacterial activity against UPEC, it may enhance UPEC infection in the bladder by promoting epithelial receptivity and local inflammation.
authors.affiliation: Department of Pediatrics Division of Biology and Biomedical Sciences.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Danka
authors.affiliation: Department of Pediatrics Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: David A
authors.initials: DA
authors.lastname: Hunstad
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D003556:Cystitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000382:microbiology / Q000473:pathology; D014552:Urinary Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000472:pathogenicity*; D019459:Urothelium / Q000382:microbiology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines
keywords: CRAMP; cathelicidin; cystitis; immune response; innate immunity; intracellular bacterial community; neutrophil; uroepithelium; uropathogenic Escherichia coli