The Immune Response to Ectromelia Virus in the Draining Lymph Node

描述（由申请方提供）：为了侵入靶器官，大量人类和动物病毒（包括正痘病毒（OPV）属的成员）破坏上皮表面，然后使用淋巴-造血（LH）途径通过区域淋巴结（LN）传播，然后通过血液传播。OPV包括天花的病因（天花病毒; VARV）、天花疫苗（牛痘病毒; VACV）和鼠痘的病因（鼠痘病毒; ECTV），主要病毒学教科书将其用作LH传播的原型。免疫学和病毒学教科书也告诉我们淋巴结的主要功能是作为淋巴细胞的启动位点。然而，我们和其他人的工作支持新出现的概念，即LN在限制病原体的LH传播方面也起着重要作用。该项目的主要目标是了解这种保护性反应如何在体内组装。具体目标是：具体目标1。明确CD 11 c + CD 11b+炎性树突状细胞（iDC）募集至D-LN并参与病毒控制的机制。具体目标2。鉴定和表征D-LN中诱导早期抗ECTV应答所需的TLR 9/MyD 88表达细胞。具体目标3。目的：探讨D-LN中CD 4 + 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的病毒，从外周淋巴血传播的控制。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.