Listeriosis in the Pregnant Mouse

怀孕小鼠的李斯特菌病

• 批准号: 7261833
• 负责人: PAUL Edwin ORNDORFF
• 金额: $ 7.09万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7261833
• 关键词: Affect; Agriculture; Animal Feed; Animals; Anti-Bacterial Agents; Applications Grants; Bacteria; Breeding; Burn injury; Cessation of life; Classification; Clinical; Clostridium botulinum; Complement; Condition; Data; Development; Dilatation and Curettage; Disease; Disease Outbreaks; Domestic Fowls; Dose; Embryo; Feces; Female; Fish Products; Food; Gram-Positive Bacteria; Growth; Health Policy; Hemochorial Placental Development; Horns; Human; Immunologic Tests; Implant; Infection; Integration Host Factors; Intestines; Invaded; Invertebrates; Lethal Dose 50; Listeria; Listeria monocytogenes; Listeriosis; Liver; Measures; Meat; Milk; Monitor; Mouse Strains; Mus; Oral; Organ; Pathogenesis; Patient currently pregnant; Peritoneal Macrophages; Placement; Predisposing Factor; Predisposition; Pregnancy; Pregnant Women; Procedures; Process; Property; Purpose; Rate; Recording of previous events; Reporting; Research; Reticuloendothelial System; Risk; Risk Assessment; Route; Score; Severity of illness; Site; Soil; Source; Spleen; Spontaneous abortion; Staging; Staining method; Stains; Time; Tissues; Vegetables; Vertebrates; Virulent; Walkers; Water; Woman; Work; base; biodefense; blastocyst; day; embryo/fetus; fetal; foodborne outbreak; foodborne pathogen; implantation; man; mouse model; natural Blastocyst Implantation; pathogen; prenatal; prophylactic; research study; sample fixation

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（由申请方提供）：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前列腺炎。在易使宿主患上寄生虫病的因素中，怀孕是女性中既不异常也不罕见的唯一情况。相对而言，人们对使孕妇更容易患病的因素知之甚少。我们最近设计了一种妊娠小鼠模型，其中经口接种后，妊娠小鼠及其未出生的后代都可以监测到绦虫病。在我们的研究中，小鼠在妊娠早期（妊娠期7.5天[总计约19.5天]）接种，在此阶段，易感性明显增加。我们的研究的这一结果和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胚泡植入，这将为细菌的不受限制的生长提供一个免疫特权位点。由于着床发生在妊娠早期，支持我们假设的实验结果很容易与支持竞争的结果区分开来，也许更流行的是，妊娠后期的全身免疫学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，我们使用了一种远系繁殖的小鼠品系（胚胎学家广泛使用），这种小鼠能够可靠地怀孕，并具有较大的窝仔。我们将采用小鼠毒性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：系统地描述妊娠小鼠的子宫内膜异位症。在不同的妊娠时间，小鼠将口服接种L.单核细胞增多症将对剂量进行分级，以获得LD 50测定结果（在一组小鼠中），并在另一组采用较低剂量的小鼠中测定器官感染性水平。胚胎和胎仔的组织学检查将与感染性研究同时进行，常规取出处死小鼠的一个子宫角，并在固定和染色后检查内容物。免疫学测试将确定怀孕如何影响怀孕动物对感染的反应的先天能力。这项补助金申请中提出的工作的好处包括一些可以立即转移到卫生政策的变化。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宫材料进行常规微生物分析），并预防妇女中的许多感染（通过向产科医生提供提示早期风险的数据）。

项目成果

Extrauterine listeriosis in the gravid mouse influences embryonic growth and development.

• DOI: 10.1371/journal.pone.0072601
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Suyemoto MM;Hamrick TS;Spears PA;Horton JR;Washington IM;Havell EA;Borst LB;Orndorff PE
• 通讯作者: Orndorff PE