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Macrophages, Granulomas, and Bacterial Persistence

巨噬细胞、肉芽肿和细菌持久性

基本信息

批准号：
9277403
负责人：
Corrella S Detweiler
金额：
$ 23.1万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9277403
关键词：
Acute Address Alpha Cell Area Bacteria Bacterial Infections Bone Marrow Brucella abortus Cell Survival Characteristics Chemicals Chronic Chronic Disease Clinical Data Development Erythrocytes Food Contamination Genetic Goals Granuloma Growth Hematopoietic Host Defense Human Immune Immune system Immunocompetent Inductively Coupled Plasma Mass Spectrometry Infection Inflammatory Ingestion Interferon Type II Iron Leishmania Leukocytes Lymphoid Tissue Methods Microbe Modeling Molecular Mus Mycobacterium leprae Mycobacterium tuberculosis Pathology Pathway interactions Phagocytes Phase Proteomics Public Health Relapse Salmonella Salmonella enterica Salmonella typhimurium Serotyping Site System Systemic infection Testing Therapeutic Tissues Toxin Typhoid Fever alpha Toxin antimicrobial base cell type contaminated water cytokine experimental study inhibitor/antagonist macrophage metal transporting protein 1 novel therapeutics pathogen uptake

项目摘要

Summary Salmonella enterica subspecies Typhimurium is a natural pathogen of mice that establishes persistent, systemic infection. Salmonella generally reside within professional phagocytes, typically macrophages, which is critical for the development of chronic infection. However, it is unclear how Salmonella can survive within a cell-type that evolved to destroy pathogens. Our lab has demonstrated that during persistent murine infections, S. Typhimurium can reside within macrophages that are hemophagocytic. Hemophagocytic macrophages (HMФs) are characterized by the ingestion of viable cells of the hematopoietic lineages, and are clinically associated with human Typhoid fever. We have also observed that by three weeks post-infection, activated macrophages, and possibly HMФs, coalesce into granulomas that harbor and appear to protect bacteria from the host immune system, potentially establishing a site at which the bacteria can survive long-term. The goal of this proposal is to determine how S. Typhimurium exploits macrophages, including HMФs and macrophages within granulomas, to withstand host defenses during acute and chronic infection. We are modeling HMФs and granulomas and the following two aims will address key questions regarding how bacteria establish and maintain colonization of tissues within HMФs and granulomas: 1) How does S. Typhimurium acquire iron from macrophages? and 2) How does S. Typhimurium survive in granulomas? How granulomas form and acquire and maintain bacteria such as Salmonella remains a poorly understood area that may be able to be targeted with therapeutics.

总结