Candida-host interactions in HIV disease: implications for oropharyngeal candidiasis

Adv Dent Res. 2011 Apr;23(1):45-9. doi: 10.1177/0022034511399284.

Abstract

Oropharyngeal candidiasis (OPC), caused primarily by Candida albicans, is the most common oral infection in HIV(+) persons. Although Th1-type CD4(+) T cells are the predominant host defense mechanism against OPC, CD8(+) T cells and epithelial cells become important when blood CD4(+) T cells are reduced below a protective threshold during progression to AIDS. In an early cross-sectional study, OPC(+) tissue biopsied from HIV(+) persons had an accumulation of activated memory CD8(+) T cells at the oral epithelial-lamina propria interface, with reduced expression of the adhesion molecule E-cadherin, suggesting a protective role for CD8(+) T cells but a dysfunction in the mucosal migration of the cells. In a subsequent 1-year longitudinal study, OPC(-) patients with high oral Candida colonization (indicative of a preclinical OPC condition), had higher numbers of CD8(+) T cells distributed throughout the tissue, with normal E-cadherin expression. In OPC(+) patients, where lack of CD8(+) T cell migration was associated with reduced E-cadherin, subsequent evaluations following successful treatment of infection revealed normal E-cadherin expression and cellular distribution. Regarding epithelial cell responses, intact oral epithelial cells exhibit fungistatic activity via an acid-labile protein moiety. A proteomic analysis revealed that annexin A1 is a strong candidate for the effector moiety. The current hypothesis is that under reduced CD4(+) T cells, HIV(+) persons protected from OPC have CD8(+) T cells that migrate to the site of a preclinical infection under normal expression of E-cadherin, whereas those with OPC have a transient reduction in E-cadherin that prohibits CD8(+) T cells from migrating for effector function. Oral epithelial cells concomitantly function through annexin A1 to keep Candida in a commensal state but can easily be overwhelmed, thereby contributing to susceptibility to OPC.

Publication types

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

MeSH terms

  • Annexin A1 / biosynthesis
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / physiology
  • Cadherins / biosynthesis
  • Candida albicans / physiology*
  • Candidiasis, Oral / complications
  • Candidiasis, Oral / immunology*
  • Candidiasis, Oral / microbiology*
  • Chemotaxis, Leukocyte
  • Epithelial Cells / microbiology
  • Gene Expression Profiling
  • HIV Infections / complications
  • HIV Infections / immunology*
  • Host-Pathogen Interactions*
  • Humans
  • Immunity, Mucosal

Substances

  • Annexin A1
  • Cadherins