Collaborative Research: Host and Pathogen Interactions in the Amphibian Disease, Chytridiomycosis

两栖动物（青蛙、蟾蜍、蝾螈）是许多生物群落的核心成员。作为蝌蚪，它们消耗溪流和池塘中的植被，成年后，它们消耗大量的昆虫猎物。反过来，它们又被蛇、鸟和小型哺乳动物吃掉。因此，许多生态系统的平衡依赖于两栖动物。目前，全世界近三分之一的两栖动物物种面临真菌皮肤病的风险，这种疾病已导致150多个物种灭绝。引起疾病的真菌与宿主有复杂的相互作用，宿主的免疫防御系统通常会控制它们。然而，许多致病真菌已经发展出免疫逃避策略。本项目将研究病原真菌损害免疫系统的机制。它将检查真菌释放的抑制淋巴细胞的因子的化学性质。如果这些因子是新颖的，它们可能被开发成控制免疫疾病的治疗剂。这项研究的成功将极大地促进我们对这种真菌用来逃避免疫清除的具体机制的理解，并可能提示其他影响人类的致病真菌所使用的新的毒力机制。水蛭壶菌（Batrachochytrium dendroatidis, Bd）是一种皮肤真菌，是世界范围内两栖动物数量下降和灭绝的原因之一。感染脊椎动物的真菌与宿主有复杂的相互作用，宿主的免疫防御通常会控制它们。然而，许多致病真菌已经发展出免疫逃避策略。本项目将研究Bd抑制淋巴细胞功能的机制。范德比尔特大学医学院、维拉诺瓦大学和格温内德梅西大学的研究人员和学生将研究由Bd和另一种两栖类真菌——蝾螈菌——产生的免疫毒性分子。目的是分离和表征由引起壶菌病的致病性Bd菌株产生的免疫调节和细胞毒性分子；(2)进一步研究Bd逃避免疫系统的机制、受影响的淋巴样细胞亚群，并确定其他非淋巴样细胞是否为Bd因子的靶点；(3)确定来自不同地理位置和不同基因组成的壶菌在代谢谱和产生对淋巴细胞和其他细胞有毒的分子方面是否存在差异。

Amphibians (frogs, toads, salamanders) are central members of many biological communities. As tadpoles, they consume vegetation in streams and ponds, and as adults, they consume large numbers of insect prey. They, in turn, are eaten by snakes, birds and small mammals. Thus, the balance of many ecosystems depends on amphibians. Currently, nearly one third of amphibian species worldwide are at risk for development of a fungal skin disease that has driven more than 150 species into extinction. Fungi that cause disease have complex interactions with their hosts, and host immune defenses generally keep them in check. However, many pathogenic fungi have developed immune evasion strategies. This project will investigate the mechanisms used by a pathogenic fungus to impair the immune system. It will examine the chemical nature of factors released by the fungus that inhibit lymphocytes. If the factors are novel, they may be developed as therapeutic agents to control immune disorders. Success in this investigation will greatly advance our understanding of the specific mechanisms that are used by this fungus to evade immune clearance and may suggest novel virulence mechanisms used by other pathogenic fungi that affect humans.Batrachochytrium dendrobatidis (Bd) is a skin fungus that is one cause of worldwide declines and extinctions of amphibians. Fungi that infect vertebrates have complex interactions with their hosts, and host immune defenses generally keep them in check. However, many pathogenic fungi have developed immune evasion strategies. This project will investigate the mechanisms by which Bd inhibits lymphocyte functions. Investigators and students at Vanderbilt University School of Medicine, Villanova University, and Gwynedd Mercy University will investigate the immunotoxic molecules produced by Bd and a second amphibian fungus, Batrachochytrium salamandrivorans. The objectives are to isolate and characterize immunomodulatory and cytotoxic molecules produced by pathogenic Bd strains responsible for chytridiomycosis; (2) to further examine the mechanisms of immune system evasion by Bd, the subsets of lymphoid cells affected, and to determine whether other non-lymphoid cells are targets of Bd factors; (3) to determine whether Batrachochytrium from different geographic locations and with differing genetic makeup vary in their metabolic profiles and production of molecules toxic to lymphocytes and other cells.