Tamm-Horsfall Protein Protects the Urinary Tract against Candida albicans

Infect Immun. 2018 Nov 20;86(12):e00451-18. doi: 10.1128/IAI.00451-18. Print 2018 Dec.

Abstract

Urinary tract infections (UTIs) caused by the human fungal pathogen Candida albicans and related species are prevalent in hospitalized patients, especially those on antibiotic therapy, with indwelling catheters, or with predisposing conditions such as diabetes or immunodeficiency. Understanding of key host defenses against Candida UTI is critical for developing effective treatment strategies. Tamm-Horsfall glycoprotein (THP) is the most abundant urine protein, with multiple roles in renal physiology and bladder protection. THP protects against bacterial UTI by blocking bacterial adherence to the bladder epithelium, but its role in defense against fungal pathogens is not yet described. Here we demonstrate that THP restricts colonization of the urinary tract by C. albicans THP binds to C. albicans hyphae, but not the yeast form, in a manner dependent on fungal expression of the Als3 adhesion glycoprotein. THP directly blocks C. albicans adherence to bladder epithelial cells in vitro, and THP-deficient mice display increased fungal burden in a C. albicans UTI model. This work outlines a previously unknown role for THP as an essential component for host immune defense against fungal urinary tract infection.

Keywords: Als3; Candida albicans; Tamm-Horsfall protein; urinary tract infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / pathogenicity*
  • Candidiasis / immunology*
  • Candidiasis / urine
  • Cell Line
  • Female
  • Fungal Proteins / genetics
  • Humans
  • Hyphae / pathogenicity
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Urinary Tract / microbiology*
  • Urinary Tract Infections / immunology*
  • Urinary Tract Infections / microbiology
  • Uromodulin / immunology*
  • Uromodulin / pharmacology
  • Urothelium / microbiology

Substances

  • ALS3 protein, Candida albicans
  • Fungal Proteins
  • Umod protein, mouse
  • Uromodulin