Regulation of B cell responses to West Nile Virus Infections
Regulation of B cell responses to West Nile Virus Infections
批准号:
7746284
负责人:
Edward A Clark
金额:
$31.7万
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
项目状态:
已结题
起止时间:
2009-05-01 至 2014-04-30
关键词:
AblationAffectAnimalsAntibodiesAntibody FormationAttenuatedB-Lymphocyte SubsetsB-LymphocytesBacteriaBone MarrowCD22 geneCategoriesCell LineageCellsChimera organismDendritic CellsDevelopmentDiamondDiseaseDisease OutcomeE proteinEncapsulatedEventFlavivirusGoalsHumanHumoral ImmunitiesImmuneImmune responseImmunityImmunizationImmunoglobulin GImmunoglobulin MIn VitroInfectionInfectious AgentInflammatoryInterferon Type IInterferon-alphaKnock-outKnockout MiceLeadLifeMadagascarMemory B-LymphocyteMolecularMonitorMusNational Institute of Allergy and Infectious DiseasePlayPredispositionProcessProductionPublic HealthRegulationRoleSerumSpleenStructure of germinal center of lymph nodeT-LymphocyteTestingTexasTimeTreatment ProtocolsVaccine DesignVaccinesVirusVirus DiseasesWest Nile virusanti-IgGbasecytokinedesignin vivoinsightlymph nodesmigrationneutralizing antibodypathogenprogramsresponsesubcutaneous
中文摘要
本提案的主要目标是阐明先天免疫感知机制的过程
英文摘要
A major goal of this proposal is to elucidate processes by which innate immune sensing mechanisms
program B lineage cells to produce protective anti-West Nile virus (WNV) IgM and IgG antibodies. Humoral
immunity to WNV is both necessary and sufficient to protect hosts from disease, however, the early events
that coordinate the initial innate and subsequence adaptive antibody (Ab) responses to WNV are not well
understood. We will elucidate how dendritic cells (DCs) and B cells respond to WNV and how rapid IgM and
IgG anti-WNV neutralizing Abs develop. We hypothesize that initial innate programming of DC subsets
dictate both the quality and the duration of protective Ab responses to WNV. To investigate this hypothesis
we will conduct the following Specific Aims: Aim 1: We will compare the course of pathogenic WNV Texas
(WN-TX) and attenuated WNV Madagascar (WN-MAD) strains early after in vivo infection. We propose that
high and low pathogenic WNVs differ in how they infect, alter and program DCs. We will quantify changes
early after infection in DC subset numbers, survival, cytokine production and infection. With Project 1, we
will determine what innate immune factors regulate initial DC responses and susceptibility to WNV infection
by comparing DC responses and infection in wildtype (WT) mice vs. C3 and IPS-1 KO mice Using mixed
bone marrow (BM) chimeras, in which DCs have been ablated, we will determine how DC ablation or the
absence in DCs of IPS-1, TLR-3 or other innate immune factors affects early events after WNV infection.
Aim 2: To determine the molecular and cellular requirements for the development of rapid IgM neutralizing
antibody responses to WNV. To determine the role of marginal zone (MZ) B cells in protective IgM immunity
to WNV, we will assess IgM responses and susceptibility of MZ B cell-deficient CD22 KO and Notch2fl/fl
conditional KO mice. DCs play a pivotal role in rapid IgM responses to encapsulated bacteria; using mixed
BM chimeras, in which DCs have been ablated, we will determine how DC ablation or the absence in DCs of
IPS-1, BAFF or other innate immune factors affects the development of neutralizing IgM Ab responses. Aim
3: We will investigate if MZ B cells are required for immune IgM to promote protective IgG immunity. Delivery
of Ag to MZ-associated DCs can lead to a strong IgG antibody response. We will examine if delivery of WNV
E protein to MZ DCs can induce IgM and IgG neutralizing Ab responses, and if so whether this form of Ag
delivery can be used to induce protective, sterilizing immunity to WNV. These studies will lead to new
insights into how best to design vaccines to WNV and other flaviviruses.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Development of Novel CD180-Based Cancer Immunotherapeutics
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批准号:10381384
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项目类别:
-
资助金额:$39.8万
-
财政年份:2022
-
负责人:Edward A Clark
-
依托单位:
Mouse Resource Core
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批准号:8811087
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项目类别:
-
资助金额:$36.75万
-
财政年份:2015
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负责人:Edward A Clark
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依托单位:
Establishing and characterizing BAFF RFP reporter and BAFF knockin mice
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批准号:8468991
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项目类别:
-
资助金额:$8.9万
-
财政年份:2012
-
负责人:Edward A Clark
-
依托单位:
Establishing and characterizing BAFF RFP reporter and BAFF knockin mice
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批准号:8353277
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项目类别:
-
资助金额:$8.9万
-
财政年份:2012
-
负责人:Edward A Clark
-
依托单位:
Dendritic cells, Mucosal Immunity and C-type Lectins
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批准号:6852485
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项目类别:
-
资助金额:$38.0万
-
财政年份:2005
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负责人:Edward A Clark
-
依托单位:
Dendritic cells, Mucosal Immunity and C-type Lectins
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批准号:7410149
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项目类别:
-
资助金额:$35.63万
-
财政年份:2005
-
负责人:Edward A Clark
-
依托单位:
Dendritic cells, Mucosal Immunity and C-type Lectins
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批准号:7596450
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项目类别:
-
资助金额:$35.63万
-
财政年份:2005
-
负责人:Edward A Clark
-
依托单位:
Dendritic cells, Mucosal Immunity and C-type Lectins
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批准号:7223471
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项目类别:
-
资助金额:$36.03万
-
财政年份:2005
-
负责人:Edward A Clark
-
依托单位:
Dendritic cells, Mucosal Immunity and C-type Lectins
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批准号:7050592
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项目类别:
-
资助金额:$37.11万
-
财政年份:2005
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
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批准号:7224169
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项目类别:
-
资助金额:$34.13万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
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批准号:6743213
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项目类别:
-
资助金额:$36.0万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
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批准号:7056670
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项目类别:
-
资助金额:$35.15万
-
财政年份:2003
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负责人:Edward A Clark
-
依托单位:
B CELL IMMUNOTHERAPY IN MACAQUES
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批准号:6940082
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项目类别:
-
资助金额:$14.14万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
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批准号:6610827
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项目类别:
-
资助金额:$38.5万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
-
批准号:8299146
-
项目类别:
-
资助金额:$42.92万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
-
批准号:8096672
-
项目类别:
-
资助金额:$42.94万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Programming protective immunity by targeting antigens to the CD180 receptor
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批准号:8979329
-
项目类别:
-
资助金额:$43.5万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
-
批准号:8481497
-
项目类别:
-
资助金额:$40.34万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
-
批准号:6891901
-
项目类别:
-
资助金额:$36.0万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
Dendritic Cell-Associated C-Type Lectins
-
批准号:7984203
-
项目类别:
-
资助金额:$43.38万
-
财政年份:2003
-
负责人:Edward A Clark
-
依托单位:
海外基金