Listeriosis in the Pregnant Mouse

怀孕小鼠的李斯特菌病

• 批准号: 7144250
• 负责人: PAUL Edwin ORNDORFF
• 金额: $ 7.3万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7144250
• 关键词: Listeria; Listeria infections; female; pregnancy

DESCRIPTION (provided by applicant): The purpose of the research proposed in this RO3 application is to better understand how pregnancy predisposes gravid animals to listeriosis. Amongst the factors that predispose a host to listeriosis, pregnancy stands out as the only condition that is neither abnormal nor rare amongst females. Comparatively little is known about factors that render the pregnant female more susceptible to disease. We have recently devised a gravid mouse model in which listeriosis can be monitored in both the pregnant mouse and her unborn offspring following oral inoculation. In our studies, mice were inoculated unusually early in gestation (7.5 gestational days [of a total of about 19.5]), and at this stage an increased susceptibility was readily apparent. This and other results from our studies led us to a hypothesis: Increased disease severity in the gravid mouse will be concomitant with blastocyst implantation, which will provide an immunologically privileged site for unrestricted bacterial growth. Since implantation occurs very early in pregnancy, experimental results favoring our hypothesis will be easily distinguished from results supporting a competing, and perhaps more prevailing, notion that systemic immunological changes late in pregnancy are responsible for increased disease severity. In our proposed studies, we use an out-bred mouse strain (utilized extensively by embryologists) that becomes pregnant reliably and has large litters. We will employ a mouse-virulent Listeria monocytogenes strain and employ the natural (oral) inoculation route. We have one specific aim: A systematic characterization of listeriosis in the gravid mouse. At various gestational times, mice will be orally inoculated with L. monocytogenes. Doses will be graded to obtain an LD50 determination (in one set of mice), and organ infectivity levels will be determined in another set in which a lower dose will be employed. Histological examination of embryos and fetuses will be carried out concurrently with the infectivity studies by routinely removing one uterine horn of a sacrificed mouse and examining the contents following fixation and staining. Immunological tests will determine how pregnancy affects the innate ability of the gravid animal to respond to infection. Benefits from the work proposed in this grant application include some that are immediately transferable into changes in health policy. For example, experimental support for our hypothesis could influence the recommended clinical procedures associated with miscarriage (by encouraging a routine microbiological analysis of expelled embryos and dilatation and curettage material) and forestall many infections in women (by acquainting obstetricians with data suggesting an early risk).

描述（由申请人提供）：本RO3申请中提出的研究目的是更好地了解妊娠如何使妊娠动物易患李斯特菌病。在使宿主易患李斯特菌病的因素中，怀孕是唯一在女性中既不异常也不罕见的情况。相对而言，使孕妇更容易患病的因素所知甚少。我们最近设计了一种妊娠小鼠模型，在该模型中，李斯特菌病可以在怀孕小鼠和未出生的后代中进行监测。在我们的研究中，小鼠在妊娠期异常早地接种（妊娠期7.5天[总共约19.5天]），在这个阶段易感性明显增加。这和我们研究的其他结果使我们提出了一个假设：妊娠小鼠疾病严重程度的增加将伴随着囊胚植入，这将为不受限制的细菌生长提供免疫特权。由于植入发生在妊娠早期，支持我们假设的实验结果将很容易与支持另一种观点的结果区分开来，这种观点认为，妊娠后期的全身免疫变化是导致疾病严重程度增加的原因。在我们提出的研究中，我们使用了一种异种繁殖的小鼠品系（胚胎学家广泛使用），它可以可靠地怀孕并且产仔量大。我们将采用小鼠毒力强的单核细胞增生李斯特菌菌株，并采用自然（口服）接种途径。我们有一个特定的目标：在妊娠小鼠李斯特菌病的系统表征。在不同的妊娠期，小鼠将口服接种单核细胞增生乳杆菌。将对剂量进行分级，以获得LD50的测定（在一组小鼠中），并在另一组使用较低剂量的小鼠中确定器官感染性水平。胚胎和胎儿的组织学检查将与感染性研究同时进行，通过常规切除一只牺牲的小鼠的子宫角，并检查固定和染色后的内容物。免疫测试将确定怀孕如何影响怀孕动物对感染的先天反应能力。本赠款申请中提出的工作所带来的好处包括一些可立即转化为卫生政策变化的好处。例如，对我们假设的实验支持可能会影响与流产相关的推荐临床程序（通过鼓励对排出的胚胎和扩张和刮除材料进行常规微生物分析），并预防妇女中的许多感染（通过让产科医生了解提示早期风险的数据）。