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.
疾病预防控制中心估计,在美国发生了约30万例莱姆病和约2000例巴贝虫病 每年莱姆病是由伯氏疏螺旋体螺旋体引起的, 在美国,巴贝西虫(Babesiophyti)(这里简称为Bm)是巴贝西虫病的主要病原体。出现 的B。在北美和欧洲不断扩大的地区,伯氏菌-Bm合并感染已成为主要的 近十年来的健康问题。在合并感染期间,这些病原体的协同或拮抗作用 尚未被描述。B。伯氏菌-Bm合并感染的患者表现出持续存在的更广泛的症状 比感染了B的病人要长。伯多菲力一个人。合并感染的患者通常需要住院治疗, 疾病在某些情况下是致命的。了解这些病原体相互之间以及对宿主的影响 将最终导致制定更好的诊断、保护和治疗战略。 迄今为止进行的有限的小鼠研究显示Bm-B的结果相互矛盾。布格多费里公司 不同品系小鼠的感染。C3 H小鼠是研究合并感染影响的理想选择,因为这 菌株表现出与人类相似的莱姆病和巴贝西虫病表现。我们的初步数据 显示Bm感染引起C3 H小鼠贫血、肝肿大和脾肿大,并导致 脾T和B细胞耗竭。这些变化与Bm-和B的降低有关。 共感染小鼠和两者中的伯氏特异性抗体:各种组织的定殖增加, 增强的炎症性莱姆病如果Bm感染仍然未被发现和治疗, 合并感染的人类可能导致患者长期痛苦,并可能导致 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B影响。易感C3 H小鼠中的burgdorferi基因表达、存活率和持久性, B的影响。burgdorferi对降低Bm寄生虫血症的作用。根据我们的初步研究, 假设:(i)宿主性别和年龄是Bm-B发病过程中重要生物学变量。 (ii)Bm对脾T和B细胞的消耗降低了总体抗体产生 影响B的动力学。伯氏菌清除,并增加莱姆病的严重程度,而刺激 先天性免疫反应由B。burgdorferi减少Bm寄生虫血症,和(iii)调节宿主反应 通过Bm诱导B中的特异性基因表达。使螺旋体、组织 定植和炎性疾病。我们将:(1)确定小鼠性别和年龄对莱姆病的影响 Bm-B期间的疾病和巴贝虫病。(2)测定序贯B治疗的效果。 莱姆病的burgdorferi/Bm感染,以及(3)鉴定莱姆病期间特异性产生的抗原蛋白。 可能促进长期B的合并感染。burgdorferi持久性更好地了解合并感染 将提供对人类疾病的深入了解,并确定持续性莱姆病的有用抗原标记。

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
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Nikhat Parveen其他文献

Nikhat Parveen的其他文献

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{{ 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:
    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:
    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:
    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:

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