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Impact of bacterial infection on myeloid dendritic cell development

细菌感染对骨髓树突状细胞发育的影响

基本信息

批准号：
8575047
负责人：
ELIZABETH HILTBOLD SCHWARTZ
金额：
$ 44.4万
依托单位：
AUBURN UNIVERSITY AT AUBURN
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8575047
关键词：
Activities of Daily Living Address Affect Animals Antigen-Presenting Cells Antigens Bacteria Bacterial Infections Bone Marrow Cell physiology Cells Communicable Diseases Dendritic Cell Vaccine Dendritic Cells Development Disease Environment Gap Junctions Goals Granulocyte-Macrophage Colony-Stimulating Factor Growth ITGAX gene Immature Monocyte Immune Tolerance Immune response Immunosuppression Immunosuppressive Agents Immunotherapeutic agent In Vitro Infection Inflammation Inflammatory Investigation Lead Listeria Listeria monocytogenes Listeriosis Lymphoid Malignant Neoplasms Measures Myelogenous Myeloid Cells Myeloid Progenitor Cells Natural Immunity Pathway interactions Phenotype Process Research Role Serum Staging Stimulus Suppressor-Effector T-Lymphocytes T cell response Testing Transcriptional Regulation Vaccine Therapy Vaccines adaptive immunity bactericide base cell type clinical application cytokine design fighting in vivo insight killings monocyte pathogen progenitor public health relevance response trafficking tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Dendritic cells offer tremendous potential in clinical applications where modulating immune responses are desired. Thanks to their potent ability to stimulate T cell responses, DC are under intense investigation as vaccines for a variety of diseases, and have shown particular promise in the cancer arena. DC are a diverse group of cells with distinct phenotypes, and functions representative of their unique subset and lineage. GM-CSF has been used successfully for years to generate large numbers of DC for study in vitro and is still the predominant cytokine used to generated DC for vaccines. DC that are developed and differentiated through GM-CSF activity are thought to represent a distinct myeloid lineage and the immediate precursors of DCs are monocytes. Upon infection with a variety of pathogens including Listeria monocytogenes, a surge in GM-CSF is observed in the serum of infected animals. However, the function of myeloid progenitor cell types in the infectious disease process remains incompletely defined. Therefore with this proposal we will test the hypothesis that infection of poorly developed myeloid cells (common myeloid progenitors and monocyte/dendritic cell progenitors) with Listeria will inhibit the overall immune response by imparting immunosuppressive function and enhancing the growth and spread of bacteria. To test this hypothesis we propose two specific aims: 1) To determine how infection of myeloid cells at distinct stages of development affects their function as antigen presenting cells. And 2) To determine how the developmental status of myeloid cells affects the fate of Listeria within the cell.

描述（由申请人提供）：树突状细胞在需要调节免疫应答的临床应用中提供了巨大的潜力。由于其刺激T细胞应答的强大能力，DC作为多种疾病的疫苗正在进行深入研究，并且在癌症竞技场中显示出特别的前景。DC是一组具有不同表型的多样化细胞，其功能代表其独特的亚群和谱系。多年来，GM-CSF已成功用于产生大量DC用于体外研究，并且仍然是用于产生DC用于疫苗的主要细胞因子。通过GM-CSF活性发育和分化的DC被认为代表不同的髓系，并且DC的直接前体是单核细胞。在感染包括单核细胞增生李斯特菌在内的多种病原体后，在感染动物的血清中观察到GM-CSF激增。然而，骨髓祖细胞类型在感染性疾病过程中的功能仍然不完全确定。因此，通过该提议，我们将测试以下假设：李斯特菌感染发育不良的骨髓细胞（普通骨髓祖细胞和单核细胞/树突状细胞祖细胞）将通过赋予免疫抑制功能和增强细菌的生长和扩散来抑制整体免疫应答。为了验证这一假设，我们提出了两个具体的目标：1）确定在不同发育阶段的骨髓细胞感染如何影响其作为抗原呈递细胞的功能。和2）确定骨髓细胞的发育状态如何影响细胞内李斯特菌的命运。