The innate Immune Response to Mousepox at the Site

然后，一场“竞赛”接踵而至，在这场竞赛中，复制的病毒试图“超过”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之前控制感染 发展一种适应性反应。在项目1中，我们将检查 先天免疫系统，以遏制鼠痘感染，鼠痘是一种由皮疹引起的致命老鼠疾病 病毒(ECTV)，一种独有的小鼠病原体。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。这三个特定的目标将检查细胞 它们是减缓ECTV在感染部位的系统性传播所必需的，化学诱导剂可以 介导它们向感染部位的迁移，以及两者使用的细胞生物学机制 病毒与免疫系统在病毒-细胞相互作用过程中。在目标1中，我们将描述细胞 在耐药或易感小鼠中渗透到ECTV感染部位并鉴定先天免疫 减慢ECTV系统性传播所需的效应细胞类型，并允许 可以清除感染的适应性反应。在这个目标中，我们还将检查效应器函数 是先天免疫细胞所需的，以延缓ECTV感染。在目标2中，我们将确定趋化因子 和趋化因子受体在耐药或易感小鼠的ECTV感染部位表达，以及 趋化因子是吸引先天效应细胞所必需的，这些细胞可以减缓病毒的复制和传播。 我们还将研究ECTV编码的细胞迁移的免疫调节剂在先天性 对病毒的反应，并将在体内确定这些基因的靶点。在目标3中，我们将研究 ECTV和天然免疫细胞在体外的相互作用，主要集中在巨噬细胞吞噬，这有 最近被描述为正痘病毒的感染方式。巨噬细胞增多症有一个重要的 在采样细胞外溶质以启动适应性免疫反应方面的作用，我们将 检查其对环境采样的贡献，以启动先天反应。我们还将 研究TLR9；，一种生存所需的先天受体向大胞体的转运 ECTV挑战赛。这个项目的结果将提供一个关于天生反应的全面图景 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.