Cellular and molecular mechanisms involving SLAMF1 during pulmonary fungal infection
肺部真菌感染过程中涉及SLAMF1的细胞和分子机制
基本信息
- 批准号:10738468
- 负责人:
- 金额:$ 19.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-19 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AbbreviationsAddressAlveolarAntibodiesBlastomyces dermatitidisBone MarrowCD4 Positive T LymphocytesCause of DeathCellsColony-forming unitsDataDefectDendritic CellsDevelopmentEffector CellEndowmentEpithelial CellsExclusionFamilyFutureGrowthHematopoieticHourImmuneIn VitroInfectionInnate Immune ResponseKnowledgeLeukocytesLungLung infectionsLymphocyteLymphoid CellMediatingMedicalMicrobeModelingMolecularMucous MembraneMusMycosesMyeloid CellsNatural ImmunityNatural Killer CellsNeutrophil ActivationNitric OxidePathway interactionsPhagocytesPharmaceutical PreparationsPopulationProductionPublishingReactive Oxygen SpeciesReceptor SignalingReportingResistanceRoleSignal TransductionStainsStromal CellsT-LymphocyteTestingTherapeuticUnited StatesVaccinesWild Type MouseWorkYeastsantimicrobialcombatdesignfungusin vivoinnovationinsightmicrobialmonocytemouse modelneutrophilnovelnovel therapeutic interventionpathogenpathogenic funguspathogenic microbereceptorrespiratoryrestraintsensortherapeutically effectivevaccine development
项目摘要
PROJECT SUMMARY/ABSTRACT
Lung cellular resistance against microbes requires a signaling network involving stroma and innate myeloid
and lymphoid cells. To date, the signaling receptors and pathways are incompletely understood. Signaling
Lymphocyte Molecule Family (SLAMF) receptors are widely expressed among hematopoietic cells and lung
epithelial cells making them ideal candidates to orchestrate phagocyte killing of microbes. We recently reported
that during pulmonary infection with the fungus Blastomyces dermatitidis (Bd), SLAMF1 is required for innate
immunity and dispensable for priming vaccine-induced CD4+ Tcells. In preliminary data, we found that
SLAMF1 is required for killing of the yeast by neutrophils and monocytes in vivo, but the receptor is dispensible
for killing in vitro. These findings suggest that extrinsic, SLAMF1 dependent signals activate phagocytes to kill
yeast in vivo.
In this application, we propose to elucidate where and how SLAMF1 receptors endow phagocytes with the
ability to kill yeast in vivo during pulmonary fungal infection. We hypothesize that innate lymphocytes and
CCR2+ monocytes are required for SLAMF1-mediated neutrophil activation. We also posit that SLAMF1
mediates its function through homophilic (SLAMF1:SLAMF1) interactions between innate lymphocytes
and monocytes or through direct sensing of the yeast by SLAMF1. We provide strong preliminary data to
support our hypotheses. By using a panel of antibodies directed against 17 pulmonary leukocyte populations,
we found SLAMF1 staining on CD4+TCR+, TCR+, MAIT cells and Ly6Chi CCR2+ monocytes at 16 hours
post-infection. Our workplan in Aim 1 offers approaches that will elucidate the requirement of SLAMF1 on
lymphoid, myeloid or stromal cells for activation of neutrophil killing of yeast. In Aim 2, we will define the mode
of SLAMF1 action by distinguishing between SLAMF1 homophilic interactions among cells that express the
receptor vs. direct sensing of yeast by SLAMF1. Our work will identify new mechanisms of receptor-mediated
activation of innate effector cells and lay the groundwork for subsequent studies to advance detailed
mechanistic insight into how SLAMF1 orchestrates signaling and activation of neutrophils, as these cells are
the most potent effector to combat fungal and other microbial pathogens. This knowledge will provide the basis
for developing and designing new strategies for therapeutic treatments against fungi, and other pathogenic
microbes that require innate immunity for pathogen restraint.
项目摘要/摘要
肺细胞对微生物的抵抗需要一个涉及基质和天然髓系的信号网络
和淋巴样细胞。到目前为止,对信号受体和信号通路的了解还不完全。信令
淋巴细胞分子家族(SLAMF)受体在造血细胞和肺中广泛表达
上皮细胞使它们成为协调吞噬细胞杀死微生物的理想候选者。我们最近报道了
在肺部感染皮炎芽孢杆菌(Bd)时,SLAMF1是先天需要的
对于疫苗诱导的CD4+T细胞的免疫和可有可无。在初步数据中,我们发现,
SLAMF1是中性粒细胞和单核细胞在体内杀死酵母所必需的,但受体是必需的。
因为在体外杀人。这些发现表明,依赖于SLAMF1的外在信号激活吞噬细胞杀死
体内的酵母菌。
在这个应用中,我们打算阐明SLAMF1受体在哪里以及如何赋予吞噬细胞以
在肺部真菌感染期间体内杀死酵母菌的能力。我们假设先天淋巴细胞和
SLAMF1介导的中性粒细胞活化需要CCR2+单核细胞。我们还假设SLAMF1
通过先天淋巴细胞之间的嗜高性(SLAMF1:SLAMF1)相互作用来调节其功能
或通过SLAMF1直接感应酵母菌。我们提供了强有力的初步数据来
支持我们的假设。通过使用一组针对17个肺白细胞群体的抗体,
16小时后发现SLAMF1在CD_4~+T细胞受体~+、T细胞受体~+、MAIT细胞和Ly6chi CCR2~+单核细胞上表达
感染后。我们在AIM 1中的工作计划提供的方法将阐明SLAMF1对以下方面的要求
淋巴、髓系或基质细胞可激活中性粒细胞,杀死酵母菌。在目标2中,我们将定义模式
通过区分表达SLAMF1的细胞之间的SLAMF1同源相互作用来研究SLAMF1的作用
SLAMF1对酵母的受体与直接感应的比较。我们的工作将确定受体介导的新机制
激活先天效应细胞,为后续研究推进细节奠定基础
对SLAMF1如何协调信号和中性粒细胞激活的机械性洞察,就像这些细胞
对抗真菌和其他微生物病原体的最有效的效应器。这些知识将提供基础
开发和设计针对真菌和其他致病菌的治疗方法的新策略
需要先天免疫才能抑制病原体的微生物。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Marcel Wuethrich其他文献
Marcel Wuethrich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('Marcel Wuethrich', 18)}}的其他基金
Regulation of vaccine-induced anti-fungal T17 cells
疫苗诱导的抗真菌 T17 细胞的调节
- 批准号:
8194616 - 财政年份:2011
- 资助金额:
$ 19.44万 - 项目类别:
Regulation of vaccine-induced anti-fungal Th17 cells
疫苗诱导的抗真菌 Th17 细胞的调节
- 批准号:
9381740 - 财政年份:2011
- 资助金额:
$ 19.44万 - 项目类别:
Regulation of vaccine-induced anti-fungal T17 cells
疫苗诱导的抗真菌 T17 细胞的调节
- 批准号:
8450924 - 财政年份:2011
- 资助金额:
$ 19.44万 - 项目类别:
Regulation of vaccine-induced anti-fungal T17 cells
疫苗诱导的抗真菌 T17 细胞的调节
- 批准号:
8262154 - 财政年份:2011
- 资助金额:
$ 19.44万 - 项目类别:
Regulation of vaccine-induced anti-fungal T17 cells
疫苗诱导的抗真菌 T17 细胞的调节
- 批准号:
8836476 - 财政年份:2011
- 资助金额:
$ 19.44万 - 项目类别:
Regulation of vaccine-induced anti-fungal Th17 cells
疫苗诱导的抗真菌 Th17 细胞的调节
- 批准号:
9976397 - 财政年份:2011
- 资助金额:
$ 19.44万 - 项目类别:
Regulation of vaccine-induced anti-fungal T17 cells
疫苗诱导的抗真菌 T17 细胞的调节
- 批准号:
8651410 - 财政年份:2011
- 资助金额:
$ 19.44万 - 项目类别:
Priming of Antifungal T-Cells at Mucosal and Systemic Sites
粘膜和全身部位抗真菌 T 细胞的启动
- 批准号:
7540447 - 财政年份:2007
- 资助金额:
$ 19.44万 - 项目类别:
Priming of Antifungal T-Cells at Mucosal and Systemic Sites
粘膜和全身部位抗真菌 T 细胞的启动
- 批准号:
7359255 - 财政年份:2007
- 资助金额:
$ 19.44万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 19.44万 - 项目类别:
Research Grant