Protective T cell-mediated (CMI) mechanisms at the oral mucosa are poorly understood. Oropharyngeal candidiasis (OPC) is the most common oral manisfestation of HIV infection and first clinical sign of immunosuppression during progression to AIDS. It is unclear, however, what immunological events take place in the oral mucosa to promote the conversion of Candida albicans from commensal to pathogen and ultimately to the development of OPC. Clinical and laboratory investigations suggest that CMI (T cells, cytokines) is the predominant host defense mechanism against C. albicans at mucosal surfaces. The preliminary data of the PI together with clinical observations indicate that while both systemic and local immunity is important, they may function with some level of independence. The PI hypothesizes that individuals suffering from advanced HIV infection acquire OPC and other oral diseases as a result of specific changes/dysfunction(s) in the normal protective CMI at the oral mucosa that may or may not correlate with systemic CMI. To test this hypothesis, he will focus on individuals with OPC in an urban patient cohort of HIV+ individuals with considerable age, gender, and racial diversity in the HIV Outpatient Program (HOP) at LSU Medical Center and perform a cross-sectional, case-controlled study with three Specific Aims. The applicant will 1) characterize the oral CD4+/CD8+ lymphocyte profile in HIV+ individuals with and without OPC and in HIV- individuals through the molecular and immunological analysis of oral biopsy tissue; 2) characterize the orally secreted Th-related immune molecules (ie., cytokines, antibodies) in each patient group through the analysis of saliva and biopsy samples; and 3) correlate the mucosal immune profile with quantitative and qualitative measurements of viral load determined by PCR of two HIV-associated viral genes (gag and pro) in the oral cavity. Data gathered relative to the oral cavity will be correlated to levels in the systemic compartment (blood, plasma and in the supernatants of blood lymphocytes stimulated in vitro with Candida antigens). The long-term goals of this project are to better understand CMI in the oral mucosa, to define immunological events/conditions associated with the susceptibility of HIV+ individuals to OPC, and to develop immunological based strategies to enhance resistance/protection against oral pathogens during HIV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE012178-02
Application #
2897143
Study Section
AIDS and Related Research Study Section 5 (ARRE)
Project Start
1998-04-01
Project End
2002-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Quimby, K; Lilly, E A; Zacharek, M et al. (2012) CD8 T cells and E-cadherin in host responses against oropharyngeal candidiasis. Oral Dis 18:153-61
Fidel Jr, P L (2011) Candida-host interactions in HIV disease: implications for oropharyngeal candidiasis. Adv Dent Res 23:45-9
Lilly, E A; Yano, J; Fidel Jr, P L (2010) Annexin-A1 identified as the oral epithelial cell anti-Candida effector moiety. Mol Oral Microbiol 25:293-304
Pereira, H Anne; Tsyshevskaya-Hoover, Irina; Hinsley, Heather et al. (2010) Candidacidal activity of synthetic peptides based on the antimicrobial domain of the neutrophil-derived protein, CAP37. Med Mycol 48:263-72
Lilly, E A; Leigh, J E; McNulty, K M et al. (2006) Chemokine receptor expression in HIV-positive persons with oropharyngeal candidiasis. Oral Dis 12:493-9
Leigh, Janet E; McNulty, Kelly M; Fidel Jr, Paul L (2006) Characterization of the immune status of CD8+ T cells in oral lesions of human immunodeficiency virus-infected persons with oropharyngeal Candidiasis. Clin Vaccine Immunol 13:678-83
Mercante, Donald E; Leigh, Janet E; Lilly, Elizabeth A et al. (2006) Assessment of the association between HIV viral load and CD4 cell count on the occurrence of oropharyngeal candidiasis in HIV-infected patients. J Acquir Immune Defic Syndr 42:578-83
Coogan, M M; Fidel Jr, P L; Komesu, M C et al. (2006) (B1) Candida and mycotic infections. Adv Dent Res 19:130-8
Lilly, E A; Leigh, J E; Joseph, S H et al. (2006) Candida-induced oral epithelial cell responses. Mycopathologia 162:25-32
Fidel Jr, P L (2006) Candida-host interactions in HIV disease: relationships in oropharyngeal candidiasis. Adv Dent Res 19:80-4

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