Grant Number :    1R01DE017335-01

Pricipal Investigator : Sieg Scott

Project Title : Oral Defensins Bridge Innate and Adaptive Immunity

Abstract : Candida albicans is an important oral pathogen in HIV disease. Both innate and adaptive immune mechanisms likely contribute to protection from C. albicans but this protection frequently fails as HIV disease progresses. In this project, we explore the hypothesis that anti-microbial peptides known as beta defensins play an important role in C. albicans immunity not only through their anti-fungal activity at the site of infected epithelium but also through their unique potential to bridge innate and adaptive immune responses. This hypothesis stems from published observations indicating that beta defensins are chemotactic for memory T cells and antigen presenting cells and from our own observations that these peptides induce maturation of antigen presenting cells. The focus of the proposed work is centered on the interactions of beta defensin with human antigen-presenting cells including monocytes, plasmacytoid and myeloid dendritic cells. We will investigate the capacity of beta defensins to cause phenotypic and function differentiation of these important antigen-presenting cell subsets. These analyses will include evaluation of the effects of beta defensins on co-stimulatory and homing molecule expression, cytokine and chemokine production and antigen processing and presentation. Our work will emphasize the importance of beta defensins in priming antigen-presenting cells to induce potent T cell responses to C. albicans. Once we have characterized the effects of beta defensins on antigen-presenting cells, we will determine the biochemical pathways that mediate these effects. Finally, to test the hypothesis that responses to beta defensins are impaired in HIV disease, we will evaluate antigen-presenting cells from HIV-infected persons for their phenotypic and functional responses to beta defensins. These studies will increase our understanding of beta defensin biology and the role of these peptides in HIV-associated oral Candida infections.

Institution : CASE WESTERN RESERVE UNIVERSITY

Duration of Award : 15 JUL 2005 - 31 MAY 2008

Amount :



 
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