Role of galectin-3 in genital tract immunosuppression

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DESCRIPTION (provided by applicant): Human seminal plasma contains multiple immunosuppressive factors that down-regulate innate immunity in the female reproductive tract. These immunosuppressive factors function to protect spermatozoa from the female immune system. However, the immunosuppressive effects potentially increase susceptibility of the female genital tract to infection by sexually transmitted diseases, including HIV. Preliminary studies from our laboratory identified galectin-3 on prostasomes, membranous vesicles in seminal plasma that inhibit leukocyte function. Significantly, galectin-3 receptors are expressed on leukocytes, galectin-3 exhibits immunomodulatory properties, and galectin-3 functions in pathogen-host cell interactions. Therefore, we hypothesize that galectin-3 contributes to the immunosuppressive properties of prostasomes and facilitates sexually transmitted infections. The overall goal of the current project is to investigate galectin-3 function in prostasomes with specific regard to immunosuppression. The aims of the proposed project are to identify the specific galectin-3 binding ligands in prostasomes by microsequence analysis and to investigate the localization and function of galectin-3 in prostasomes. Surface localization of galectin-3 and its ligands on prostasomes will be investigated using immunoelectron microscopy and flow cytometry. The role of galectin-3 in prostasome-leukocyte adhesion will be evaluated using fluorescence microscopy and flow cytometry. Functional assays will investigate the role of galectin-3 in prostasome-mediated inhibition of lymphocyte proliferation and of reactive oxygen species (ROS) production in neutrophils. A potential regulatory mechanism of galectin-3 function in prostasomes involving a truncated galectin-3 variant will be investigated. We anticipate that improved understanding of immunosuppressive factors in seminal plasma and their effects on innate and adaptive immunity in the female genital tract will provide significant insights into STD/HIV transmission and pathogenesis and will have significant implications for future STD prevention strategies.