IMMUNE RESPONSES TO MICROSPORIDIA

对小孢子虫的免疫反应

• 批准号: 8358039
• 负责人: Elizabeth Schmidt Didier
• 金额: $ 3.72万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358039
• 关键词: Citrates; Encephalitozoon cuniculi; Funding; Grant; Immune response; Infection; Iron; Mammals; Microsporidia; Mus; National Center for Research Resources; Nitrogen; Organism; Oxygen; Parasites; Peritoneal; Peritoneal Macrophages; Primates; Principal Investigator; Reactive Nitrogen Species; Reactive Oxygen Species; Research; Research Infrastructure; Resources; Rest; Source; Supplementation; Tryptophan; United States National Institutes of Health; Wild Type Mouse; cost; inhibitor/antagonist; macrophage

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Encephalitozoon cuniculi (Phylum Microsporidia) infects a wide range of mammals, and replicates within resting macrophages. Activated macrophages, conversely, inhibit replication and destroy intracellular organisms. These studies were performed to assess mechanisms of innate immune responses expressed by macrophages to control E. cuniculi infection. Addition of reactive oxygen and nitrogen species inhibitors to activated murine peritoneal macrophages statistically significantly, rescued E. cuniculi infection ex vivo. Mice deficient in reactive oxygen species, reactive nitrogen species, or both survived ip inoculation of E. cuniculi, but carried significantly higher peritoneal parasite burdens than wild-type mice at 1 and 2 weeks post inoculation. Infected peritoneal macrophages could still be identified 4 weeks post inoculation in mice deficient in reactive nitrogen species. L-tryptophan supplementation of activated murine peritoneal macrophage cultures ex vivo failed to rescue microsporidia infection. Addition of ferric citrate to supplement iron, however, did significantly rescue E. cuniculi infection in activated macrophages and further increased parasite replication in non-activated macrophages over non-treated resting control macrophages. These results demonstrate the contribution of reactive oxygen and nitrogen species, as well as iron sequestration, to innate immune responses expressed by macrophages to control E. cuniculi infection.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 脑cuniiculi（微孢子虫）感染各种哺乳动物，并在静止巨噬细胞内复制。 激活的巨噬细胞，相反，抑制复制并破坏细胞内生物。 进行了这些研究，以评估巨噬细胞表达的先天免疫反应的机制，以控制大肠杆菌感染。 在统计学上显着地增加了活化的鼠腹膜巨噬细胞，从而在活化的鼠腹膜巨噬细胞中添加了反应性氧和氮抑制剂，从而营救了E. cuniculi感染。 缺乏活性氧，反应性氮种或两者都在cuniculi的IP接种中幸存下来，但在接种后1和2周时，与野生型小鼠相比，腹膜寄生虫负担比野生型寄生虫负担明显更高。 在反应性氮种缺乏反应性氮的小鼠后4周，仍可以发现感染的腹膜巨噬细胞。 l- tryptophan补充活化的鼠腹膜巨噬细胞培养物未能营救微孢子虫感染。 然而，加入柠檬酸铁以补充铁，在活化的巨噬细胞中确实显着挽救了Cuniculi感染，并进一步增加了未经治疗的静止对照巨噬细胞中未激活的巨噬细胞中寄生虫的复制。 这些结果证明了活性氧和氮种以及铁固相对巨噬细胞表达的先天免疫反应对控制E. cuniculi感染的贡献。