Tyrosine phosphorylation during A. phagocytophilum invasion

描述：细胞内生物操纵它们的宿主细胞以适应它们的细胞内生活方式。这些病原体通过将细菌因子引入宿主细胞来改变细胞过程。嗜吞噬细胞无形体， 引起人类粒细胞埃里希体病，是一种独特的细胞内生物，因为它是唯一的人类 在中性粒细胞中生存和繁殖的病原体。中性粒细胞在免疫系统中发挥重要作用。 免疫系统和杀死细菌非常有效。A.嗜吞噬细胞菌是个例外， 中性粒细胞。人们对A.嗜吞噬细胞菌操纵细胞过程， 中性粒细胞的生存。 全局假设是A.嗜吞噬细胞菌通过将细菌因子转移到嗜中性粒细胞中以确保其存活来操纵细胞过程。我们已经确定了一个候选细菌因子，AnkA，它可能介导这些影响。因此，A.嗜吞噬细胞菌感染中性粒细胞提供了理想的 模型来研究参与中性粒细胞生物学和细菌杀伤的途径。 目的1检测AnkA的酪氨酸磷酸化，这使得它能够与特定的宿主细胞相互作用 SH2结构域的蛋白质 目的2旨在鉴定这些宿主细胞蛋白和AnkA操纵的信号通路。 目的3研究AnkA对中性粒细胞呼吸爆发的影响。 长期目标是：1）确定A.嗜吞噬细胞菌 中性粒细胞，2）开发新的途径来操纵中性粒细胞，导致潜在的新的 治疗炎症或感染，以及3）增强我们对中性粒细胞生物学的理解， 它与免疫系统有关。 在美国，人粒细胞埃立克体病是一种新出现的蜱相关疾病， 流行区发病率仅次于莱姆病。

Description: Intracellular organisms manipulate their host cells to suit their intracellular life styles. These pathogens alter cellular processes by introducing bacterial factors into the host cell. Anaplasma phagocytophilum, which causes Human Granulocytic Ehrlichiosis, is a unique intracellular organism because it is the only human pathogen that specifically survives and multiplies in neutrophils. Neutrophils play an essential role in the immune system and kill bacteria very efficiently. A. phagocytophilum is the exception as it escapes killing by neutrophils. It is poorly understood how A. phagocytophilum manipulates the cellular processes in the neutrophil for its survival. The global hypothesis is that A. phagocytophilum manipulates cellular processes by translocating bacterial factors into the neutrophil ensuring its survival. We have identified a candidate bacterial factor, AnkA, which may mediate these effects. Consequently, A. phagocytophilum infection of neutrophils provides an ideal model to study the pathways involved in neutrophil biology and bacterial killing. Aim 1 examines the tyrosine phosphorylation of AnkA, which allows it to interact with specific host cells proteins through SH2 domains. Aim 2 seeks to identify these host cell proteins and the signaling pathways manipulated by AnkA. Aim 3 examines the effect of AnkA on the respiratory burst, the major killing pathway of the neutrophil. The long-term goals are: 1) the identification of the mechanism leading to survival of A. phagocytophilum in neutrophils, 2) the development new avenues to manipulate neutrophils, leading to potential new treatments of inflammation or infections, and 3) enhancement of our understanding of neutrophil biology as it relates to the immune system. In the Unites States, Human Granulocytic Ehrlichiosis is an emerging tick-associated disease and in endemic areas the incidence is second only to Lyme disease.