Defensins at the Interface of Male and Female Innate Immunity

加里N CherrIOS-0843649雄性和雌性天然免疫界面的防御素哺乳动物雌性生殖道具有免疫反应以保护免受外来入侵者的侵害，包括将白色血细胞吸引到该区域。 精子细胞如何克服这些防御，同时在白色血细胞的吸引中发挥作用，是生殖生物学的关键问题。 这项资助的中心假设试图将哺乳动物生殖的这两个重要步骤联系起来，形成一个统一的概念。 研究人员最近证明，在雄性生殖道中，哺乳动物精子成熟过程中，一种称为β-防御素的分子均匀地覆盖在精子的整个表面。 β-防御素是在整个动物王国中发现的先天免疫的关键效应肽。 这些肽具有有效的抗微生物活性，并作为化学引诱剂。 虽然在几种无脊椎动物中已经描述了生殖组织表达β-防御素肽，但精子表面存在β-防御素是一个新的发现，并且最近才在哺乳动物中描述。它们的存在可能反映了这些肽对内部受精的适应。 有人提出，精子相关的β-防御素，形成一个统一的表面涂层的精子，促进生育能力，首先保护精子免受免疫识别的女性生殖道，然后提供增强的先天性免疫保护，部分吸引白色血细胞。 研究人员建议通过使用小鼠模型的体内和体外实验相结合来测试这些想法。 这一创新项目将为生殖生物学中长期存在的问题提供答案，并将为哺乳动物生殖适应性变化的来源提供见解。 了解这些机制对于管理家养物种的生殖、评估野生动物的生殖适应度以及维持人类的生殖健康具有重要意义。

Gary N CherrIOS-0843649Defensins at the Interface of Male and Female Innate ImmunityThe mammalian female reproductive tract has immune responses to protect against foreign invaders, including the attraction of white blood cells to the area. How sperm cells overcome these defenses as well, and at the same time, play a role in white blood cell attraction, are key questions in reproductive biology. The central hypothesis of this grant seeks to link these two important steps of mammalian reproduction into a unifying concept. The investigators have recently demonstrated that molecules called beta-defensins uniformly coat the entire surface of mammalian sperm during maturation in the male tract. Beta-defensins are key effector peptides of innate immunity found throughout the animal kingdom. These peptides have potent antimicrobial activities and act as chemical attractants. While the expression of beta-defensin peptides by reproductive tissue has been described in several invertebrate species, the presence of beta-defensins on the sperm surface is a novel finding and has only been recently described in mammals. Their presence may reflect adaptations of these peptides for internal fertilization. It is proposed that sperm-associated beta-defensins, which form a uniform surface coat on spermatozoa, promote fertility by first protecting sperm from immunorecognition by the female reproductive tract and then providing enhanced innate immune protection in part by attracting white blood cells. The investigators propose to test these ideas through a combination of in vivo and in vitro experiments using a mouse model. This innovative project will yield answers to longstanding questions in reproductive biology and will provide insights into the sources of variation of reproductive fitness in mammals. The understanding of these mechanisms holds significance for managing reproduction in domestic species, evaluating reproductive fitness in wildlife, and maintaining reproductive health in humans.