The Immunological Consequences of Mouse Cytomegalovirus on Adipose Tissue

小鼠巨细胞病毒对脂肪组织的免疫学影响

• 批准号: 9331959
• 负责人: Nico Contreras
• 金额: $ 3.55万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-30 至 2020-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9331959
• 关键词: Acute; Address; Adenoviruses; Adipocytes; Adipose tissue; Antigens; Atherosclerosis; B-Lymphocytes; Blood Vessels; C57BL/6 Mouse; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Cellular Tropism; Chronic; Clone Cells; Cytomegalovirus; Cytomegalovirus Infections; Endocrinology; Flow Cytometry; Glucose Intolerance; Goals; HIV; Health; Human; Immune; Immune response; Immunity; Immunologics; Immunology; Infection; Inflammation; Inflammatory; Insulin Resistance; Investigation; Kinetics; Link; Lipids; Location; Metabolic; Metabolism; Modeling; Murid herpesvirus 1; Mus; Natural Killer Cells; Obesity; Parasites; Patients; Peripheral; Peripheral Blood Mononuclear Cell; Plaque Assay; Population; Recruitment Activity; Reporting; Research; Role; SIV; Salivary Glands; Site; Stromal Cells; T cell response; T-Cell Activation; T-Lymphocyte; Time; Tissues; Tropism; Trypanosoma cruzi; Vaccine Design; Viral; Viral Load result; Virus; Virus Diseases; Virus Latency; Work; cell type; cytokine; density; experimental study; knowledge base; macrophage; response; stem; tissue tropism; vaccinology; virology

Abstract Adipose tissue has long been thought to simply be a site of lipid synthesis and energy storage. However, it has become increasingly clear that the inflammatory state of adipose tissue has profound effects on host immunity and metabolism. Recent reports have demonstrated that both viruses and parasites are capable of directly infecting the adipocytes and cellular constituents of adipose tissue. Furthermore, Human Immunodeficiency Virus (HIV) is capable of becoming latent within T cells found in adipose. Cytomegalovirus (CMV), a ubiquitous betaherpesvirus, results in a persistent lifelong infection and the holy grail of CMV research has been to identify sites of latency, but no study has demonstrated the extent to which adipose tissue is infected or harbors latent and persistent virus. CMV has a broad cellular and tissue tropism, and susceptible cells are all represented within the adipose tissue. Thus, it is necessary to investigate the consequences, if any, of CMV infection within adipose. In order to understand the consequence(s) of CMV infection on adipose we will employ the C57BL/6 mouse CMV (mCMV) model of infection. The goal of this proposal is to understand the functional consequences and mechanism of spread during mCMV infection within adipose tissue. The overall hypothesis of this proposal is that mCMV disseminates to adipose tissue, replicates, establishes latency, leading to an lifelong CD8 T cell response. We will address the hypothesis and achieve the goals of this proposal by first, determining the cell type(s) that are infected within adipose tissue during infection by qPCR, plaque assay, and flow cytometry. We will also determine if mCMV is capable of becoming reactivated from within adipose tissue. Second, we will determine the kinetic expansion and contraction of mCMV specific CD8 T cells. Investigation into infection of and the role of adipose tissue during an immune response is a new and growing field, thus this work, when completed, will represent a significant advancement in our fundamental base of knowledge regarding mCMV cell tropism and persistence. The findings of this proposal will call for the consideration of adipose tissue in the context of infection, which has far reaching impact on vaccinology, immunology, virology, and endocrinology.

抽象的 长期以来，脂肪组织一直被认为只是脂质合成和能量储存的场所。然而，它有 越来越清楚的是，脂肪组织的炎症状态对宿主免疫具有深远的影响 和新陈代谢。最近的报告表明，病毒和寄生虫都能够直接 感染脂肪细胞和脂肪组织的细胞成分。此外，人体免疫缺陷 病毒 (HIV) 能够潜伏在脂肪中的 T 细胞内。巨细胞病毒（CMV）是一种普遍存在的病毒 乙型疱疹病毒会导致持续性终生感染，巨细胞病毒研究的目标是 确定潜伏位点，但没有研究证明脂肪组织被感染的程度或 含有潜伏且持久的病毒。 CMV具有广泛的细胞和组织趋向性，易感细胞均为 代表在脂肪组织内。因此，有必要调查 CMV 的后果（如果有） 脂肪内感染。为了了解 CMV 感染对脂肪的影响，我们将 采用 C57BL/6 小鼠 CMV (mCMV) 感染模型。该提案的目标是了解 脂肪组织内 mCMV 感染期间的功能后果和传播机制。整体 该提议的假设是 mCMV 传播到脂肪组织、复制、建立潜伏期， 导致终生的 CD8 T 细胞反应。我们将解决这个假设并实现这个目标 建议首先通过 qPCR 确定感染期间脂肪组织内感染的细胞类型， 斑块测定和流式细胞术。我们还将确定 mCMV 是否能够从 脂肪组织内。其次，我们将确定 mCMV 特异性 CD8 的动力学扩张和收缩 T细胞。研究脂肪组织在免疫反应过程中的感染和作用是一项新的研究 不断发展的领域，因此这项工作一旦完成，将代表我们的基础知识方面的重大进步 有关 mCMV 细胞趋向性和持久性的知识基础。该提案的调查结果将要求 在感染背景下考虑脂肪组织，这对疫苗学具有深远的影响， 免疫学、病毒学和内分泌学。