title: Candida-host interactions in HIV disease: implications for oropharyngeal candidiasis.
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.
authors: Department of Oral and Craniofacial Biology, Center of Excellence in Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, Louisiana, USA. pfidel@lsuhsc.edu
authors: P L
authors: PL
authors: Fidel
mesh_terms: D017305:Annexin A1 / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D015820:Cadherins / Q000096:biosynthesis; D002176:Candida albicans / Q000502:physiology*; D002180:Candidiasis, Oral / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D002634:Chemotaxis, Leukocyte; D004847:Epithelial Cells / Q000382:microbiology; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D018928:Immunity, Mucosal
chemical_list: D017305:Annexin A1; D015820:Cadherins