Tyrosine phosphorylation during A. phagocytophilum invasion

描述：胞内生物操纵它们的宿主细胞以适应它们在胞内的生活方式。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。吞噬细胞性无浆体， 引起人类粒细胞性埃立克体病，是一种独特的细胞内有机体，因为它是唯一的人类 在中性粒细胞中专门存活和繁殖的病原体。中性粒细胞在体内起着至关重要的作用。 免疫系统，并非常有效地杀灭细菌。吞噬细胞性细菌是个例外，因为它能逃脱杀戮。 被中性粒细胞感染。吞噬细胞性假单胞菌是如何操纵细胞过程的，目前尚不清楚。 中性粒细胞才能生存。 全球假说是吞噬艾美耳氏菌通过将细菌因子转移到中性粒细胞中来操纵细胞过程，以确保其存活。我们已经确定了一种候选细菌因子ANKA，它可能介导这些影响。因此，嗜中性粒细胞的吞噬弧菌感染提供了一种理想的 模型研究中性粒细胞生物学和细菌杀灭的途径。 目标1检测Anka的酪氨酸磷酸化，这使其能够与特定的宿主细胞相互作用 蛋白通过SH2结构域。 目标2试图确定这些宿主细胞蛋白和ANKA操纵的信号通路。 目的3研究Anka对中性粒细胞的主要杀伤途径呼吸爆发的影响。 长期目标是：1)鉴定导致吞噬细胞性弧菌存活的机制。 中性粒细胞，2)开发操纵中性粒细胞的新途径，导致潜在的新 炎症或感染的治疗，以及3)加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，人类粒细胞性埃立克体病是一种新出现的扁虱相关疾病，在 流行地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.