Tamm-Horsfall protein protects the urinary tract against Candida albicans

Alison Coady, Anissa R. Ramos, Joshua Olson, Victor Nizet, Kathryn A. Patrasa

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere00451
JournalInfection and immunity
Volume86
Issue number12
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

Keywords

  • Als3
  • Candida albicans
  • Tamm-Horsfall protein
  • Urinary tract infection

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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