Tissue specific role of IFNalpha/beta and IFNgamma in innate immuniy to prio path
IFNα/β 和 IFNγ 在先天免疫中的组织特异性作用
基本信息
- 批准号:7672130
- 负责人:
- 金额:$ 35.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-04-09 至 2014-02-28
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAntibodiesBackcrossingsBacteriaBiologyBioterrorismBoxingBreedingC57BL/6 MouseCellsCessation of lifeCollaborationsComplexDefectEngineeringFamilyFamily memberFigs - dietaryFrancisellaFrancisella tularensisGene TargetingGenesGeneticGenetic HeterogeneityGoalsHamstersHumanIFNAR1 geneIFNGR1 geneImmuneImmune responseImmunobiologyIn VitroIndividualInfectionInfection ControlInfectious AgentInterferon Type IInterferon-alphaInterferonsKnowledgeLaboratoriesLearningLeukocytesListeriaListeria monocytogenesModelingMolecular GeneticsMolecular and Cellular BiologyMonoclonal AntibodiesMusNK Cell ActivationNatural ImmunityOrganismParasitesPhysiologicalPlayPopulationProcessProtein FamilyProteinsReagentResistanceResistance to infectionRoleSpeedT-LymphocyteTestingTherapeuticTissuesUpper armViralVirusVirus DiseasesYersiniaYersinia pestisbasebiodefensecell typecongeniccytokineembryonic stem cellin vivomacrophagememberneutralizing monoclonal antibodiesneutrophilnovelpandemic diseasepathogenpreventprogramsreceptorresearch studystemvirology
项目摘要
Type I Interferons (the family of IFNa proteins and IFNp) and Type II IFN (IFNy) play central and essential
roles in promoting innate immunity against a wide variety of viruses, bacteria and parasites. The IFNs
induce not only cell-intrinsic mechanisms that protect host cells against pathogen infection but also activate a
variety of cell-extrinsic mechanisms leading to activation of NK cells, macrophages, polymorphonuclear
leukocytes and T cells that destroy infected cells. Our knowledge of IFN biology has stemmed largely from in
vitro experiments performed on IFN-responsive versus unresponsive cells and in vivo approaches in which
IFN responsiveness is globally ablated in mice through use of neutralizing or blocking monoclonal antibodies
or through disruption of genes encoding either the IFN species themselves or their respective receptors.
The physiologic relevance of these studies have been validated by the discovery of humans who have
distinct defects in either producing or responding to the various forms of IFN. However, since the receptors
for IFNa/p or IFNy are expressed on nearly all cells, we still know very little about the cell-specific functions
of these cytokines in vivo. Since the IFNs play such a key role in innate immunity, obtaining a more detailed
understanding of their common and unique effects on different cell populations is not only needed but
essential if we wish to intentionally stimulate innate immunity, either prophylactically or therapeutically, to
protect us against naturally-occurring (e.g. pandemic viral infections) or intentionally-produced (e.g.,
bioterrorism) infections. Armed with (1) an extensive understanding of IFN biology that the Schreiber lab has
gained from molecular and genetic experiments conducted over the last 28 years (2) a comprehensive
knowledge that exists within the Unanue laboratory about the immunobiology of Listeria monocytogenes
infection, and (3) the particularly broad and deep understanding of virology that the other members of this
MRCE program bring to this application, we propose to produce and study mice on a stabilized C57BL/6
genetic background that lack responsiveness to IFNa/p or IFNy in specific cell types to define the tissue
specific actions of the IFNs to infection with priority pathogens.
I型干扰素(IFNa蛋白和IFNp家族)和II型IFN(IFNy)发挥核心和必需的作用,
在促进针对多种病毒、细菌和寄生虫的先天免疫中的作用。IFNs
不仅诱导保护宿主细胞免受病原体感染细胞内在机制,而且激活
导致NK细胞、巨噬细胞、多形核细胞活化的多种细胞外源性机制
白细胞和T细胞破坏受感染的细胞。我们对干扰素生物学的了解主要来自于
对IFN-应答细胞与无应答细胞进行的体外实验和体内方法,其中
通过使用中和或阻断单克隆抗体在小鼠中全面消除IFN应答性
或通过破坏编码IFN种类本身或其各自受体的基因。
这些研究的生理相关性已经被发现的人类所证实,
在产生或响应各种形式的IFN方面存在明显缺陷。然而,由于受体
由于IFN α/β或IFN γ几乎在所有细胞上都有表达,我们对它们的细胞特异性功能仍然知之甚少
这些细胞因子在体内。由于IFN在先天免疫中起着如此关键的作用,因此获得更详细的
不仅需要了解它们对不同细胞群体的共同和独特作用,
如果我们希望有意识地刺激先天免疫,无论是免疫学上还是治疗上,
保护我们免受自然发生的(例如大流行病毒感染)或故意产生的(例如,
生物恐怖主义)感染。装备(1)广泛了解干扰素生物学,施赖伯实验室有
从过去28年进行的分子和遗传实验中获得的(2)一个全面的
Unanue实验室内关于单核细胞增生李斯特菌免疫生物学的知识
感染,和(3)特别广泛和深刻的理解病毒学的其他成员,这是
MRCE计划带来了这一应用,我们建议生产和研究小鼠在稳定的C57 BL/6
在特定细胞类型中缺乏对IFN α/β或IFN γ的反应性的遗传背景,以定义组织
IFN对感染优先病原体的具体作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ROBERT DAVID SCHREIBER其他文献
ROBERT DAVID SCHREIBER的其他文献
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{{ truncateString('ROBERT DAVID SCHREIBER', 18)}}的其他基金
DEVELOPMENT OF GENOMICS BASED PERSONALIZED CANCER IMMUNOTHERAPY
基于基因组学的个性化癌症免疫治疗的发展
- 批准号:
8887618 - 财政年份:2015
- 资助金额:
$ 35.94万 - 项目类别:
DEVELOPMENT OF GENOMICS BASED PERSONALIZED CANCER IMMUNOTHERAPY
基于基因组学的个性化癌症免疫治疗的发展
- 批准号:
9031745 - 财政年份:2015
- 资助金额:
$ 35.94万 - 项目类别:
Tissue specific role of IFNalpha/beta and IFNgamma in innate immuniy to prio path
IFNα/β 和 IFNγ 在先天免疫中的组织特异性作用
- 批准号:
8234935 - 财政年份:2011
- 资助金额:
$ 35.94万 - 项目类别:
The Molecular and Cellular Basis of Cancer Immunoediting
癌症免疫编辑的分子和细胞基础
- 批准号:
6771282 - 财政年份:2004
- 资助金额:
$ 35.94万 - 项目类别:
The Molecular and Cellular Basis of Cancer Immunoediting
癌症免疫编辑的分子和细胞基础
- 批准号:
7215633 - 财政年份:2004
- 资助金额:
$ 35.94万 - 项目类别:
The Molecular and Cellular Basis of Cancer Immunoediting
癌症免疫编辑的分子和细胞基础
- 批准号:
6888072 - 财政年份:2004
- 资助金额:
$ 35.94万 - 项目类别:
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