The Immune Response to Ectromelia Virus in the Draining Lymph Node

引流淋巴结对湿疹病毒的免疫反应

• 批准号: 8891575
• 负责人: Luis J Sigal
• 金额: $ 60.59万
• 依托单位: RESEARCH INST OF FOX CHASE CAN CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8891575
• 关键词: Animal Viruses; Antigens; Antiviral Agents; Blood; Bone Marrow; CD4 Positive T Lymphocytes; CXCL9 gene; Cell Adhesion Molecules; Cells; Chimera organism; Dendritic Cells; Distant; Educational process of instructing; Epithelial; Event; Generations; Genes; Goals; Health; Hematogenous; Hematopoietic; Human; Human Virus; ITGAM gene; ITGAX gene; Immigration; Immune; Immune response; Immunity; Immunology; Immunophenotyping; Infection; Infectious Ectromelia; Inflammatory; Inflammatory Response; Interferons; Invaded; Lead; Lymphocyte; Microscopy; Modeling; Mouse Pox Virus; Mus; Mutant Strains Mice; Natural Killer Cells; Organ; Orthopoxvirus; Pathway interactions; Peripheral; Play; Population; Recruitment Activity; Resistance; Role; Route; Signal Transduction; Site; Skin; Smallpox; Smallpox Vaccine; Smallpox Viruses; Surface; Systemic infection; Textbooks; Time; Vaccine Adjuvant; Vaccinia virus; Virus; Virus Diseases; Work; autocrine; chemokine; cytokine; density; in vivo; lymph nodes; member; mutant; novel; novel vaccines; paracrine; pathogen; research study; response; sensor; tool; transcription factor; virology

DESCRIPTION (provided by applicant): To invade target organs, a large number of human and animal viruses, including members of the orthopoxvirus (OPV) genus, breach epithelial surfaces and then use a lympho-hematogenous (LH) route of dissemination through the regional lymph node (LN) and then the blood. OPVs include the cause of smallpox (variola virus; VARV), the smallpox vaccine (vaccinia virus; VACV), and the cause of mousepox (ectromelia virus; ECTV) that the main virology textbooks use as the archetype for LH dissemination. Immunology and virology textbooks also teach us that the primary function of LNs is to serve as sites of lymphocyte priming. However, work by us and others support the emerging concept that LNs also play an essential role in restricting the LH dissemination of pathogens. The major goal of this project is to understand the how this protective response is assembled in vivo. The Specific Aims are: Specific Aim 1. To determine the mechanism whereby CD11c+ CD11b+ inflammatory dendritic cells (iDC) are recruited to the D-LN and contribute to virus control. Specific Aim 2. To identify and characterize the TLR9/MyD88 expressing cells required for the induction of the early anti-ECTV response in the D-LN. Specific Aim 3. To investigate the mechanisms of cytolytic CD4+ T cell induction in the D-LN. With these three Aims we will discover novel mechanisms that permit the control in the D-LN of a virus that spreads lympho- hematogenously from the periphery. This should be applicable to many pathogenic viruses.

描述（由申请人提供）：为入侵目标器官，包括正托病毒（OPV）属的大量人类和动物病毒，透明上皮表面，然后使用淋巴神经元（LH）通过区域淋巴结（LN）和血液进行淋巴神经病（LH）途径。 OPV包括天花（Variola病毒； VARV），天花疫苗（Vaccinia Virus; vacv）的原因，以及主要的病毒学教科书用作LHEDENSEMAINTIAN的主要病毒学教科书用作主要病毒学教科书的原因。免疫学和病毒学教科书还告诉我们，LNS的主要功能是充当淋巴细胞启动的部位。但是，我们和其他人的工作支持新兴的概念，即LNS在限制病原体的LH传播中也起着至关重要的作用。该项目的主要目标是了解如何在体内组装这种保护性响应。具体目的是：特定目标1。确定CD11C+ CD11b+炎症树突状细胞（IDC）的机制，并募集到D-LN并有助于病毒控制。具体目标2。识别和表征D-LN早期抗ECTV响应所需的TLR9/MYD88表达细胞。具体目的3。研究D-LN中细胞溶解CD4+ T细胞诱导的机理。通过这三个目标，我们将发现新的机制，这些机制允许在病毒的D-LN中控制，该病毒从周围传播淋巴肿瘤。这应该适用于许多病毒病毒。