Host Pathways that Enable /Salmonella/ Replication Within Hemophagocytic Macropha

使/沙门氏菌/在噬血细胞巨噬细胞内复制的宿主途径

基本信息

批准号：
8418684
负责人：
Corrella S Detweiler
金额：
$ 19.06万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-15 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8418684
关键词：
Acute Bacteria Biological Assay Biological Models Blood Platelets Bone Marrow Cell Separation Cells Characteristics Chronic Clinical Communicable Diseases Cryptococcus neoformans Data Disease Erythrocytes Escherichia coli Gene Expression Gene Expression Profile Genes Genus Mycobacterium Goals Gram-Negative Bacteria Health Hematopoietic Histiocytosis haematophagic Histoplasma capsulatum Human Immune system Infection Inflammation Inflammatory Response Intestines Leishmania Leukocytes Life Lipids Liver Maps Methodology Microbe Molecular Monitor Mus Mycobacterium tuberculosis Oral Pathology Pathway interactions Patients Pattern Phagocytosis Phenotype Play Protozoa RNA Interference Reading Regulator Genes Regulatory Pathway Relative (related person)Research Role Salmonella Salmonella enterica Salmonella typhimurium Signal Pathway Signal Transduction Spleen Testing Tissues Typhoid Fever Vesicle Virus Work cell type fungus high reward high risk influenzavirus insight lymph nodes macrophage mouse genome new therapeutic target next generation sequencing novel pathogen precursor cell research study response success therapeutic development therapy development transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Many bacterial pathogens important to human health evade the immune system by living within white blood cells. Salmonella enterica, a species of gram-negative bacteria that includes the causative agent of human typhoid fever, resides within a class of white blood cells called macrophages. We have demonstrated that in mice, S. enterica subspecies Typhimurium (Salmonella) resides and replicates within hemophagocytic macrophages (HM?s), which are macrophages that have engulfed erythrocytes, platelets, leukocytes and their precursor cells. Our long-term goal is to determine how Salmonella and HM?s interact to cause disease. Mice infected with Salmonella are a natural host-pathogen model system encountered in the wild. Salmonella causes an acute infection in mice that typically resolves into a chronic infection, and the disease course resembles that of typhoid fever. The bacteria colonize the spleen, liver, and the lymph nodes that drain the intestine. We demonstrated the presence of HM?s within the spleen, liver and bone marrow of Salmonella - infected mice and identified HM?s containing Salmonella as late as eight weeks post-infection in the liver, when persistent infection has been established. In Preliminary Studies we developed a flow cytometric assay to identify and separate HM?s from other cell types. This novel methodology along with established approaches enables new exploration of the role of HM?s in disease. The objective of the current proposal is to identify regulatory pathways within HM?s needed to make these cells permissive for Salmonella replication. Completion of the Aims within has potential use in the development of treatments that modulate hemophagocytosis and influence the course of inflammation in infectious and non-infectious circumstances.

描述（由申请人提供）：许多对人类健康至关重要的细菌病原体通过生活在白细胞中逃避免疫系统。沙门氏菌Enterica是一种革兰氏阴性细菌，其中包括人伤寒的病因，它位于一类称为巨噬细胞的白细胞中。我们已经证明，在小鼠中，肠道葡萄球菌（沙门氏菌）居住并重复出现在血型巨噬细胞（HM？s）内，哪些巨噬细胞吞噬了红细胞，血小板，白细胞，白细胞及其前体细胞。我们的长期目标是确定沙门氏菌和HM的相互作用如何引起疾病。感染沙门氏菌的小鼠是野外遇到的天然宿主 - 病原体模型系统。沙门氏菌会导致小鼠的急性感染，通常会溶解成慢性感染，并且疾病病程类似于伤寒。细菌定居脾脏，肝脏和耗尽肠道的淋巴结。我们证明了沙门氏菌感染的小鼠的脾，肝脏和骨髓内的HM s存在，并在肝脏感染后八周内确定了HM含有沙门氏菌的HM含量，并确定了持续性感染。在初步研究中，我们开发了一种流式细胞术测定，以识别并将HM与其他细胞类型分开。这种新颖的方法以及既定的方法可以新探索HM在疾病中的作用。当前建议的目的是确定HM所需的调节途径，以使这些细胞允许使用沙门氏菌复制。目的的完成可能在调节胞吞作用并影响传染性和非感染状况的炎症过程中的治疗过程中潜在使用。