Bacteriophage pathobiology of inflammatory bowel disease
炎症性肠病的噬菌体病理学
基本信息
- 批准号:10601011
- 负责人:
- 金额:$ 61.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-06 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:Abdominal PainAdherent Invasive Escherichia coliAdjuvantAffectAntibody titer measurementAntigensAntiviral ResponseBacteriaBacterial InfectionsBacteriophagesBiological AssayCaudoviralesCellsCellular ImmunityChronicColiphagesColitisCrohn&aposs diseaseDiarrheaDiseaseEngineeringEscherichia coliFamilyFatigueFeverGerm-FreeGoalsHealthHomeostasisHumanImmuneImmune responseImmune systemImmunityImmunologic StimulationImmunologistIndividualInfectionInflammationInflammatoryInflammatory Bowel DiseasesInflammatory ResponseInoviridaeMalnutritionMediatingMicrobeModelingMulti-Drug ResistanceMusMyoviridaePathogenesisPattern RecognitionPattern recognition receptorPersonsPhysiologicalPlayPopulationPredispositionProbioticsProductionProphagesReceptor ActivationRoleRouteSafetyScienceScientistSerumSeveritiesSiphoviridaeStimulusTLR3 geneTailTestingTherapeutic InterventionUlcerative ColitisVaccinatedVaccinationVaccinesVirulenceVirusWorkWound Infectioncell typecytokinedefined contributionfecal transplantationgastrointestinalgut inflammationgut microbiomegut microbiotaimmunoregulationmicrobial productsmicrobiotamouse modelmurine colitisnovelnovel therapeutic interventionpathogenpreventprophylactictreatment strategyvaccine strategy
项目摘要
Bacteriophage pathobiology of inflammatory bowel disease
Ulcerative colitis and Crohn’s disease are types of inflammatory bowels diseases (IBD) that affect millions of
people around the world. IBD is characterized by chronic progressive intestinal inflammation which is driven in
large part by disruption of the gut microbiome in susceptible individuals. Infection by pathogens such as adherent
invasive Escherichia coli (AIEC) in particular exacerbates IBD pathogenesis. Treatment strategies that restore
gut microbiota homeostasis such as probiotics and fecal microbiota transplantation show promise in treating IBD.
These treatment strategies, however, focus primarily on the bacterial component of the microbiota. The most
abundant entities in the gut are the bacteriophages (phages) that infect these bacteria. Even though it is
recognized that phage populations expand during IBD exacerbations, we know surprisingly little about how
phages contribute to IBD pathogenesis. Our recent work demonstrates that diverse species of phages are
recognized by pattern recognition receptors on human and murine immune cells. We find filamentous phages
trigger TLR3-dependent inflammatory responses that promote bacterial infection in a wound infection model.
Vaccinating against these phages was an effective strategy at preventing wound infection. We also find that
tailed Caudovirales phages stimulate TLR9-dependent inflammation in the gut. Based on these observations,
we hypothesize that phages produced by adherent invasive E. coli modulate immune responses in ways that
exacerbate IBD. To test this hypothesis, we have established a team of microbiologists, immunologists, and
vaccine scientists. In Aim 1, we will characterize how inflammatory conditions stimulate bacteriophage replication
in the gut. In Aim 2, we will determine how broadly bacteriophages are recognized by innate pattern recognition
receptors. In Aim 3, we will develop and optimize an anti-bacteriophage vaccine strategy to treat IBD. Together,
these aims represent a novel and timely approach in understanding not only how phages affect IBD
pathogenesis, but for evaluating the safety and efficacy of phage therapy to treat multidrug-resistant bacterial
infections.
炎症性肠病的噬菌体病理生物学
溃疡性结肠炎和克罗恩病是影响数百万人的炎症性肠病(IBD)的类型。
全世界的人。IBD的特征是慢性进行性肠道炎症,
很大程度上是由于易感个体的肠道微生物组被破坏。病原体感染,如粘附性
侵袭性大肠杆菌(AIEC)尤其加剧IBD发病机制。恢复的治疗策略
肠道微生物群稳态如益生菌和粪便微生物群移植显示出治疗IBD的前景。
然而,这些治疗策略主要集中在微生物群的细菌成分上。最
肠道中丰富的实体是感染这些细菌的噬菌体(噬菌体)。即使它是
虽然我们认识到噬菌体群体在IBD恶化期间扩张,但我们对如何扩张知之甚少,
炎症因子参与IBD的发病机制。我们最近的工作表明,不同种类的植物
由人和鼠免疫细胞上的模式识别受体识别。我们发现丝状真菌
触发TLR3依赖性炎症反应,促进伤口感染模型中的细菌感染。
针对这些细菌接种疫苗是预防伤口感染的有效策略。我们还发现
尾状尾病毒目刺激肠道中的TLR9依赖性炎症。根据这些观察,
我们推测粘附侵袭性E.大肠杆菌调节免疫反应的方式,
加重IBD。为了验证这一假设,我们建立了一个由微生物学家、免疫学家和
疫苗科学家在目标1中,我们将描述炎症条件如何刺激噬菌体复制
在肚子里。在目标2中,我们将确定先天模式识别对噬菌体的识别范围
受体。在目标3中,我们将开发和优化治疗IBD的抗噬菌体疫苗策略。在一起,
这些目标代表了一种新的和及时的方法,不仅可以了解炎症是如何影响IBD的,
致病机制,但用于评估噬菌体疗法治疗多重耐药细菌的安全性和有效性
感染.
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Immune-bacteriophage interactions in inflammatory bowel diseases.
- DOI:10.1016/j.coviro.2021.04.010
- 发表时间:2021-08
- 期刊:
- 影响因子:5.9
- 作者:Gogokhia L;Round JL
- 通讯作者:Round JL
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June Louise Round的其他文献
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{{ truncateString('June Louise Round', 18)}}的其他基金
Microbiota-immune interactions that promote intestinal homeostasis
促进肠道稳态的微生物群-免疫相互作用
- 批准号:
10428606 - 财政年份:2021
- 资助金额:
$ 61.28万 - 项目类别:
Microbiota-immune interactions that promote intestinal homeostasis
促进肠道稳态的微生物群-免疫相互作用
- 批准号:
10211299 - 财政年份:2021
- 资助金额:
$ 61.28万 - 项目类别:
Microbiota-immune interactions that promote intestinal homeostasis
促进肠道稳态的微生物群-免疫相互作用
- 批准号:
10626869 - 财政年份:2021
- 资助金额:
$ 61.28万 - 项目类别:
Mechanisms of fungal involvement during intestinal disease
肠道疾病期间真菌参与的机制
- 批准号:
10161779 - 财政年份:2020
- 资助金额:
$ 61.28万 - 项目类别:
Bacteriophage pathobiology of inflammatory bowel disease
炎症性肠病的噬菌体病理学
- 批准号:
10159896 - 财政年份:2020
- 资助金额:
$ 61.28万 - 项目类别:
Bacteriophage pathobiology of inflammatory bowel disease
炎症性肠病的噬菌体病理学
- 批准号:
10357959 - 财政年份:2020
- 资助金额:
$ 61.28万 - 项目类别:
Mechanisms of fungal involvement during intestinal disease
肠道疾病期间真菌参与的机制
- 批准号:
10615244 - 财政年份:2020
- 资助金额:
$ 61.28万 - 项目类别:
Mechanisms of fungal involvement during intestinal disease
肠道疾病期间真菌参与的机制
- 批准号:
10358640 - 财政年份:2020
- 资助金额:
$ 61.28万 - 项目类别:
Exploring the function of a novel, microbiota-regulated gene in T cells
探索 T 细胞中新型微生物调节基因的功能
- 批准号:
8621566 - 财政年份:2014
- 资助金额:
$ 61.28万 - 项目类别:
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