New mechanism of oral immunity to mucosal candidiasis in hyper-IgE syndrome

Mucosal Immunol. 2011 Jul;4(4):448-55. doi: 10.1038/mi.2011.5. Epub 2011 Feb 23.


Oropharyngeal candidiasis (OPC, thrush) is an opportunistic infection caused by the commensal fungus Candida albicans. An understanding of immunity to Candida has recently begun to unfold with the identification of fungal pattern-recognition receptors such as C-type lectin receptors, which trigger protective T-helper (Th)17 responses in the mucosa. Hyper-IgE syndrome (HIES/Job's syndrome) is a rare congenital immunodeficiency characterized by dominant-negative mutations in signal transducer and activator of transcription 3, which is downstream of the Th17-inductive cytokines interleukin (IL)-6 and IL-23, and hence patients with HIES exhibit dramatic Th17 deficits. HIES patients develop oral and mucocutaneous candidiasis, supporting a protective role for Th17 cells in immunity to OPC. However, the Th17-dependent mechanisms of antifungal immunity in OPC are still poorly defined. An often unappreciated aspect of oral immunity is saliva, which is rich in antimicrobial proteins (AMPs) and exerts direct antifungal activity. In this study, we show that HIES patients show significant impairment in salivary AMPs, including β-defensin 2 and Histatins. This tightly correlates with reduced candidacidal activity of saliva and concomitantly elevated colonization with Candida. Moreover, IL-17 induces histatins in cultured salivary gland cells. This is the first demonstration that HIES is associated with defective salivary activity, and provides a mechanism for the severe susceptibility of these patients to OPC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenosine Monophosphate / immunology
  • Adenosine Monophosphate / metabolism
  • Adolescent
  • Adult
  • Candida albicans / immunology
  • Candidiasis / complications*
  • Candidiasis / immunology*
  • Child
  • Female
  • Gene Expression Regulation / immunology
  • Histatins / immunology
  • Histatins / metabolism
  • Humans
  • Immunity, Mucosal
  • Job Syndrome / complications*
  • Job Syndrome / immunology*
  • Male
  • Middle Aged
  • Mouth Mucosa / immunology*
  • Mouth Mucosa / microbiology*
  • Saliva / immunology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Young Adult
  • beta-Defensins / immunology
  • beta-Defensins / metabolism


  • Histatins
  • beta-Defensins
  • Adenosine Monophosphate