Role of galectin-3 in genital tract immunosuppression

描述（由申请方提供）：人精浆含有多种免疫抑制因子，可下调女性生殖道中的先天免疫。这些免疫抑制因子的功能是保护精子免受女性免疫系统的侵害。然而，免疫抑制作用可能会增加女性生殖道对性传播疾病（包括艾滋病毒）感染的易感性。我们实验室的初步研究确定了半乳糖凝集素-3对前列腺体，精浆中抑制白细胞功能的膜囊泡。值得注意的是，半乳糖凝集素-3受体在白细胞上表达，半乳糖凝集素-3表现出免疫调节特性，并且半乳糖凝集素-3在病原体-宿主细胞相互作用中起作用。因此，我们假设半乳糖凝集素-3有助于前列腺体的免疫抑制特性，并促进性传播感染。目前项目的总体目标是研究半乳糖凝集素-3在前列腺体中的功能，特别是免疫抑制。该项目的目的是通过微序列分析鉴定前列腺体中的特异性半乳糖凝集素3结合配体，并研究半乳糖凝集素3在前列腺体中的定位和功能。半乳糖凝集素-3及其配体的前列腺体的表面定位将使用免疫电子显微镜和流式细胞术进行研究。将使用荧光显微镜和流式细胞术评价半乳糖凝集素-3在前列腺体-白细胞粘附中的作用。功能测定将研究半乳糖凝集素-3在前列腺酶体介导的抑制淋巴细胞增殖和中性粒细胞中活性氧（ROS）产生中的作用。将研究半乳糖凝集素-3在前列腺体中的功能的潜在调节机制，所述前列腺体涉及截短的半乳糖凝集素-3变体。我们预计，精浆中的免疫抑制因子及其对女性生殖道先天性和适应性免疫的影响的进一步了解将为STD/HIV传播和发病机制提供重要的见解，并将对未来的STD预防策略产生重大影响。

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.