The innate Immune Response to Mousepox at the Site

然后是一场“竞赛”，即复制病毒试图“超越”宿主的免疫系统。 在感染的早期阶段，先天免疫系统必须在感染前控制感染。 发展适应性反应。在项目1中，我们将研究 先天免疫系统可遏制鼠痘感染，鼠痘是一种由脱肢症引起的致命小鼠疾病 病毒（ECTV），一种小鼠独有的病原体。这个系统是独一无二的，因为它允许我们检查 易感和耐药小鼠品系的先天反应。三个特定目标将检查细胞 在感染部位减缓ECTV的全身传播所需的化学引诱物， 介导它们迁移到感染部位和细胞生物学机制， 在病毒-细胞相互作用期间，病毒和免疫系统。在目标1中，我们将表征细胞 在抗性或易感小鼠中浸润到ECTV感染部位，并鉴定先天性免疫 这些效应细胞类型是减缓ECTV系统性传播并允许ECTV发展所需的。 可以清除感染的适应性反应在这个目标中，我们也将研究效应器功能， 是先天免疫细胞阻止ECTV感染所必需的。在目标2中，我们将确定趋化因子 和趋化因子受体表达在耐药或易感小鼠的ECTV感染部位， 趋化因子是吸引先天效应细胞所必需的，这些细胞减缓病毒的复制和传播。 我们还将研究ECTV编码的细胞迁移免疫修饰剂在先天性免疫缺陷中的作用。 反应的病毒，并将确定这些基因在体内的目标。在目标3中，我们将研究 体外ECTV和先天性免疫细胞的相互作用，主要集中在巨胞饮作用， 最近被描述为正痘病毒的感染模式。巨胞饮作用对 在细胞外溶质的采样中起作用，以启动适应性免疫反应，我们将 研究其对环境采样的贡献，以启动先天反应。我们还将 检查TLR 9向巨胞饮体的运输，TLR 9是一种先天性受体， ECTV激发。该项目的结果将提供一个全面的图片的先天反应 到外周病毒感染。

and then a "race" ensues, in which the replicating virus attempts to "outpace" the host's immune system. In the early phases of infection, the innate immune system must contain the infection prior to the development of an adaptive response. In Project 1 we will examine the mechanisms that are used by the innate immune system to contain infection with mousepox, a lethal mouse disease caused by ectromelia virus (ECTV), an exclusive mouse pathogen. This system is unique because it allows us to examine the innate response in susceptible and resistant mouse strains. The three Specific Aims will examine the cells that are required to slow the systemic spread of ECTV at the site of infection, the chemoattractants that mediate their migration to the site of infection and the cell biological mechanisms that are used by both the virus and the immune system during virus-cell interaction. In Aim 1 we will characterize the cellular infiltrate to the site of ECTV infection in resistant or susceptible mice and identify the innate immune effector cell types that are required to slow the systemic spread of ECTV and allow the development of an adaptive response that can clear the infection. In this aim we will also examine the effector functions that are required by innate immune cells to retard ECTV infection. In Aim 2 we will determine the chemokines and chemokine receptors expressed at the site of ECTV infection in resistant or susceptible mice, and the chemokines that are essential to attract innate effector cells that slow replication and spread of the virus. We will also study the role of immune modifiers of cellular migration encoded by ECTV in the innate response to the virus, and will identify the targets of these genes in vivo. In Aim 3 we will study the interaction of ECTV and innate immune cells in vitro, focusing primarily upon macropinocytosis, which has recently been described as the mode of infection of orthopoxviruses. Macropinocytosis has an important role in the sampling of extracellular solute for initiation of an adaptive immune response and we will examine its contribution to sampling of the environment for initiation of an innate response. We will also examine the trafficking to macropinosomes of TLR9;,an innate receptor that is required for survival from ECTV challenge. The results from this Project will provide a comprehensive picture of the innate response to a peripheral virus infection.