Interactions of tick-borne pathogens, Borrelia burgdorferi and Babesia microti with the mammalian host using rodent model of co-infections

使用啮齿动物共感染模型研究蜱传病原体、伯氏疏螺旋体和田鼠巴贝虫与哺乳动物宿主的相互作用

基本信息

  • 批准号:
    10467070
  • 负责人:
  • 金额:
    $ 39.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-08-09 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

The CDC estimates that ~300,000 cases of Lyme disease and ~2000 cases of babesiosis occur in the USA every year. Lyme disease is caused by Borrelia burgdorferi spirochetes while the protozoan parasite Babesia microti (referred to as Bm here) is the major causative agent of babesiosis in the USA. Emergence of B. burgdorferi-Bm co-infections in expanding regions of North America and Europe has become a major health concern in the last decade. Synergism or antagonism of these pathogens during co-infections has not yet been described. B. burgdorferi-Bm co-infected patients show more extensive symptoms that persist longer than patients infected with B. burgdorferi alone. Co-infected patients often need hospitalization, and disease in some cases is fatal. Understanding the effects of these pathogens on each other and on the host will ultimately lead to development of better diagnostic, protective and treatment strategies. Limited murine studies conducted until now showed contradictory outcomes of Bm-B. burgdorferi co- infections in different mouse strains. C3H mice are ideal to study the impact of co-infections because this strain exhibits both Lyme disease and babesiosis manifestations similar to humans. Our preliminary data shows that infection with Bm causes anemia, hepatomegaly, and splenomegaly in C3H mice and results in depletion of splenic T and B cells. These changes are associated with a decrease in Bm- and B. burgdorferi-specific antibodies in co-infected mice and both: increased colonization of various tissues and enhanced inflammatory Lyme disease. If Bm infection remains undetected and untreated, such changes in co-infected humans could result in prolonged suffering of patients and could potentially contribute to post- treatment Lyme disease syndrome. We propose to carry out the first extensive study to understand the impact of Bm on B. burgdorferi gene expression, survival and persistence in the susceptible C3H mice and the effect of B. burgdorferi on reducing Bm parasitemia. Based upon our preliminary studies, we hypothesize that: (i) host sex and age are significant biological variables in pathogenesis during Bm-B. burgdorferi co-infection, (ii) depletion of splenic T and B cells by Bm reduces overall antibody production affecting kinetics of B. burgdorferi clearance and increases severity of Lyme disease while stimulation of innate immune response by B. burgdorferi reduces Bm parasitemia, and (iii) modulation of host response by Bm induces specific gene expression in B. burgdorferi to allow long-term survival of spirochetes, tissues colonization, and inflammatory disease. We will: (1) determine the effect of sex and age of mice on Lyme disease and babesiosis during Bm-B. burgdorferi co-infections, (2) determine the effect of sequential B. burgdorferi/Bm infections on Lyme disease, and (3) identify antigenic proteins produced specifically during co-infections that may facilitate long-term B. burgdorferi persistence. A better understanding of co-infections will provide an insight into human disease and identify useful antigenic markers for persistent Lyme disease.
美国疾病控制与预防中心估计,美国约有30万例莱姆病病例和约2000例巴贝斯病病例 每年都有。莱姆病是由伯氏疏螺旋体引起的,而原虫是寄生虫 微小巴贝斯虫(BM)是美国巴贝斯虫病的主要病原体。浮现 在北美和欧洲不断扩大的地区,伯氏杆菌和BM混合感染已成为主要的 在过去的十年里,人们对健康问题感到担忧。这些病原体在合并感染过程中的协同或拮抗作用 还没有被描述。Burgdorferi-BM混合感染的患者表现出更广泛的症状,并持续存在 比单独感染伯氏杆菌的患者时间更长。合并感染的患者通常需要住院治疗,而且 在某些情况下,疾病是致命的。了解这些病原体对彼此和对寄主的影响 最终将导致制定更好的诊断、保护和治疗战略。 到目前为止进行的有限的小鼠研究表明,BM-B的结果相互矛盾。Burgdorferi co. 感染不同品系的小鼠。C3H小鼠是研究混合感染影响的理想动物,因为 菌株表现出与人类相似的莱姆病和巴贝斯虫病的表现。我们的初步数据 研究表明,感染BM会导致C3H小鼠贫血、肝肿大和脾肿大,并导致 脾T、B细胞耗竭。这些变化与BM-和B的减少有关。 混合感染小鼠和两者中的伯氏杆菌特异性抗体:各种组织和组织的定植增加 炎症性莱姆病加重。如果BM感染仍未被发现和治疗,这种变化在 混合感染的人类可能导致患者长时间的痛苦,并可能导致后 治疗莱姆病综合征。我们建议进行第一次广泛的研究,以了解 BM对伯氏杆菌在易感C3H小鼠和小鼠体内表达、存活和存活的影响 白僵菌降低骨髓原虫血症的作用。根据我们的初步研究,我们 假设:(I)宿主性别和年龄是BM-B发病机制中的重要生物学变量。 Burgdorferi混合感染,(Ii)BM耗尽脾T和B细胞减少总体抗体产生 影响伯氏杆菌清除的动力学并增加莱姆病的严重程度 伯氏杆菌的先天免疫反应可降低BM寄生虫血症,以及(Iii)调节宿主反应 BM在伯氏杆菌中诱导特异性基因表达以允许螺旋体、组织长期存活 殖民和炎症性疾病。我们将:(1)测定小鼠的性别和年龄对莱姆病的影响 BM-B期间的疾病和巴贝斯虫病。Burgdorferi混合感染,(2)确定序贯B。 伯氏杆菌/BM感染对莱姆病的影响,以及(3)鉴定在莱姆病期间产生的抗原蛋白。 可能促进伯氏杆菌长期持续存在的混合感染。更好地了解合并感染 将提供对人类疾病的洞察,并为持续性莱姆病识别有用的抗原标记物。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Borrelia burgdorferi colonizes the mammary glands of lactating C3H mice: does not cause congenital Lyme disease.
伯氏疏螺旋体定植于哺乳期 C3H 小鼠的乳腺:不会引起先天性莱姆病。
  • DOI:
    10.1016/j.micinf.2023.105241
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    Velásquez,ClaraVásquez;Moustafa,MohamedAM;Rocha,SandraC;Parveen,Nikhat
  • 通讯作者:
    Parveen,Nikhat
Transmission Cycle of Tick-Borne Infections and Co-Infections, Animal Models and Diseases.
  • DOI:
    10.3390/pathogens11111309
  • 发表时间:
    2022-11-08
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Rocha SC;Velásquez CV;Aquib A;Al-Nazal A;Parveen N
  • 通讯作者:
    Parveen N
Lessons Learned for Pathogenesis, Immunology, and Disease of Erythrocytic Parasites: Plasmodium and Babesia.
Protozoan co-infections and parasite influence on the efficacy of vaccines against bacterial and viral pathogens.
  • DOI:
    10.3389/fmicb.2022.1020029
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    Akoolo, Lavoisier;Rocha, Sandra C.;Parveen, Nikhat
  • 通讯作者:
    Parveen, Nikhat
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Nikhat Parveen其他文献

Nikhat Parveen的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Nikhat Parveen', 18)}}的其他基金

Functional assessment of TprC/D and TprK proteins of syphilis causing spirochete, Treponema pallidum
梅毒螺旋体、梅毒螺旋体 TprC/D 和 TprK 蛋白的功能评估
  • 批准号:
    10477191
  • 财政年份:
    2021
  • 资助金额:
    $ 39.25万
  • 项目类别:
Interactions of tick-borne pathogens, Borrelia burgdorferi and Babesia microti with the mammalian host using rodent model of co-infections
使用啮齿动物共感染模型研究蜱传病原体、伯氏疏螺旋体和田鼠巴贝虫与哺乳动物宿主的相互作用
  • 批准号:
    10226964
  • 财政年份:
    2019
  • 资助金额:
    $ 39.25万
  • 项目类别:
Borrelia burgdorferi-glycosaminoglycan interactions and Lyme disease pathogenesis
伯氏疏螺旋体-糖胺聚糖相互作用和莱姆病发病机制
  • 批准号:
    8493982
  • 财政年份:
    2011
  • 资助金额:
    $ 39.25万
  • 项目类别:
Borrelia burgdorferi-glycosaminoglycan interactions and Lyme disease pathogenesis
伯氏疏螺旋体-糖胺聚糖相互作用和莱姆病发病机制
  • 批准号:
    8291968
  • 财政年份:
    2011
  • 资助金额:
    $ 39.25万
  • 项目类别:
Borrelia burgdorferi-glycosaminoglycan interactions and Lyme disease pathogenesis
伯氏疏螺旋体-糖胺聚糖相互作用和莱姆病发病机制
  • 批准号:
    8871664
  • 财政年份:
    2011
  • 资助金额:
    $ 39.25万
  • 项目类别:
Borrelia burgdorferi-glycosaminoglycan interactions and Lyme disease pathogenesis
伯氏疏螺旋体-糖胺聚糖相互作用和莱姆病发病机制
  • 批准号:
    8186098
  • 财政年份:
    2011
  • 资助金额:
    $ 39.25万
  • 项目类别:
Borrelia burgdorferi-glycosaminoglycan interactions and Lyme disease pathogenesis
伯氏疏螺旋体-糖胺聚糖相互作用和莱姆病发病机制
  • 批准号:
    8718996
  • 财政年份:
    2011
  • 资助金额:
    $ 39.25万
  • 项目类别:
A unique approach to identify markers for congenital syphilis and neurosyphilis
识别先天性梅毒和神经梅毒标记物的独特方法
  • 批准号:
    7812566
  • 财政年份:
    2010
  • 资助金额:
    $ 39.25万
  • 项目类别:
DbpA/B proteins of Borrelia burgdorferi & Lyme arthritis
伯氏疏螺旋体的 DbpA/B 蛋白
  • 批准号:
    6570683
  • 财政年份:
    2003
  • 资助金额:
    $ 39.25万
  • 项目类别:
DbpA/B proteins of Borrelia burgdorferi & Lyme arthritis
伯氏疏螺旋体的 DbpA/B 蛋白
  • 批准号:
    6708371
  • 财政年份:
    2003
  • 资助金额:
    $ 39.25万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 39.25万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了