GOAT MODEL OF EHRLICHIA CHAFFEENSIS RESERVOIR INFECTION

我们的长期目标是了解查菲氏肠杆菌和其他埃立克生物是如何在自然界中维持的。作为追求这一目标的一个主要目标，本申请提出将国内目标发展为查菲埃希氏菌脊椎动物感染的模型。中心假设是，在以实验室为基础的查菲斯棘球绦虫宿主感染动态研究中，家山羊可以作为白尾鹿亟需的替代品。这项拟议研究背后的理论基础是，山羊可以为白尾鹿提供一个更好的宿主感染的实验室模型。山羊的天性比鹿容易驯服得多，而且它们在一生中都很容易被人摆弄。这种温顺的性质使感染研究的设计有了更大的自由度，并降低了与处理相关的伤害的风险。此外，山羊比鹿更可用于研究，由于受控近亲繁殖，实验动物之间可以获得更高程度的相似性，它们很容易在没有扁虱(因此没有接触埃利希菌)的设施中饲养，并且有更多种类的实验室试剂可用于山羊的工作。简而言之，一旦开发出脊椎动物水库感染的山羊模型，就可以设计和进行用鹿进行的实验，这是不可能的。为了实现这一应用的目标，我们将追求四个具体目标：(1)确定查菲埃希氏菌感染是如何在家山羊中发展和维持的，(2)评估在没有再暴露的情况下查菲埃希氏菌感染的持久性，(2)在没有再次暴露的情况下评估查菲埃希氏菌感染的持续性，(3)评估山羊对查菲埃希氏菌同源菌株多次再次攻击的反应，以及(4)通过扁虱饲养将查菲埃希氏菌从受感染的家养山羊传播到未感染的家养山羊。在这项研究完成后，我们希望通过描述国内目标范围内的查菲埃希氏菌的感染过程，开发出一种替代的反刍动物模型，用于研究脊椎动物水库宿主内的查菲埃希氏菌。此外，我们还将评估山羊在没有再次暴露的情况下感染的持久性以及山羊对多次、频繁再次暴露的反应，并建立了山羊通过扁虱饲养感染的自然模型。该模型的发展及其在未来实验中的应用将有助于了解查菲氏艾美耳球虫在天然野生水库宿主中的感染动态。新的控制策略可能会产生。

Our long range goal is to understand how E. chafeensis and other ehrlichial organisms are maintained in nature. As a major objective in pursuit of this goal, this application proposes to develop the domestic goal as a model of E. chafeensis vertebrate infection. The central hypothesis is that domestic goats can serve as a much-needed surrogate to white-tailed deer in laboratory based studies of E. chafeensis reservoir infection dynamics. The rationale behind the proposed research is that goats could provide a superior laboratory model of reservoir host infection to white-tailed deer. Goats have a much more tractable nature than deer and they remain easy to handle throughout their life. This docile nature allows greater latitude in the design of infection studies and reduces the risk of handling-associated injury. In addition, goats are more widely available than deer for research, a higher degree of similarity can be obtained between experimental animals due to controlled inbreeding, they are easily raised in tick-free (and thus Ehrlichia-exposure free) facilities, and a larger variety of laboratory reagents are available for work with goats. In short, a goat model of vertebrate reservoir infection, once developed, would allow design and conduct of experiments not readily possible with deer. To accomplish the objective of this application, we will pursue four specific aims: (1) determine how E. chafeensis infection develops and is maintained in domestic goats, (2) evaluates the persistence of E. chafeensis infection in the absence of re-exposure, domestic goats, (2) evaluate the persistence of E. chafeensis infection in the absence of re-exposure, (3) evaluate the response of goats to multiple re-challenge with a homologous strain of E. chafeensis, and (4) transmit E. chafeensis from infected to naive domestic goats via tick feeding. At the completion of this research we expect to have developed an alternative ruminant model for studying E. chafeensis within the vertebrate reservoir host by characterizing the course of E. chafeensis infection within the domestic goal. Additionally, we will have evaluated both the persistence of infection in goats in the absence of re-exposure and the response of goats to multiple, frequent re-exposure, as well as have developed a natural model of infection in goats via tick feeding. The development of this model and its subsequent application in future experiments will facilitate understanding about the dynamics of E. chafeensis infection in the natural wild reservoir host. New control strategies could result.