The Immune Response to Ectromelia Virus in the Draining Lymph Node

描述(申请人提供)：为了入侵目标器官，大量的人类和动物病毒，包括正痘病毒(OPV)属的成员，突破上皮表面，然后使用淋巴-血液传播途径，通过区域淋巴结(LN)，然后是血液。OPV包括天花的起因(天花病毒；VARV)、天花疫苗(痘苗病毒；VACV)和鼠痘的起因(皮疹病毒；ECTV)，这些都是主要病毒学教科书用作黄体生成素传播的原型。免疫学和病毒学教科书也告诉我们，LNS的主要功能是作为淋巴细胞启动的场所。然而，我们和其他人的工作支持了一个新兴的概念，即LNS在限制病原体的黄体生成素传播方面也发挥了重要作用。该项目的主要目标是了解这种保护性反应是如何在体内组装的。具体目的有：1.明确CD11c+CD11b+炎性树突状细胞(IDC)被募集到D-LN并参与病毒控制的机制。特定目的2.鉴定和鉴定在D-LN中诱导早期抗ECTV反应所需的TLR9/MyD88表达细胞。具体目的3.探讨D-LN中细胞溶解的CD4+T细胞的诱导机制。有了这三个目标，我们将发现新的机制，允许在D-LN控制一种从外围通过淋巴-血液传播的病毒。这应该适用于许多致病病毒。

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.