Dynamics of neutrophil trafficking in Granulocytic Anaplasmosis

粒细胞无形体病中中性粒细胞运输的动态

• 批准号: 9294504
• 负责人: Jennifer Lynn Johns
• 金额: $ 6.68万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9294504
• 关键词: Dynamics; neutrophil; trafficking; Granulocytic; Anaplasmosis

Project Summary/Abstract: Anaplasma phagocytophilum is a tick-borne obligate intracellular bacterial pathogen and the agent of granulocytic anaplasmosis in humans and animals. A. phagocytophilum primarily infects neutrophils (PMNs), subverting normal PMN apoptosis and killing mechanisms to facilitate bacterial proliferation. In contrast to endotoxin-positive bacterial infections, A. phagocytophilum infection induces neutropenia despite increased bone marrow (BM) granulopoiesis. The implication is that this granulocytotropic pathogen may fundamentally alter the upstream regulation of PMN mobilization, the downstream regulation of PMN release from BM and the systemic trafficking and homing of PMN during infection. Neutropenia and hematopoietic alterations likely contribute to the serious clinical complications of A. phagocytophilum infection, including opportunistic infections, but the mechanisms involved in altered PMN trafficking during A. phagocytophilum infection are largely unknown. Our global hypothesis is that A. phagocytophilum infection and pathogen replication perturb normal PMN trafficking and may ultimately facilitate pathogen-PMN interaction and enhance bacterial propagation. Infection-induced production of granulocyte colony stimulating factor (G-CSF) and interleukin-8 (IL-8) will be investigated as upstream regulators of PMN mobilization from BM via effects on intermediate signaling and integrin-mediated interactions. Systemic PMN trafficking and splenic homing will be defined using sophisticated imaging strategies. Mechanisms of PMN trafficking including chemotactic gradients and integrin-mediated interactions in the spleen will be determined. Our goal is to define mechanisms of infection-induced PMN trafficking and to determine their role in the innate immune response and clinical consequences of disease. The KO1 award would support Dr. Jennifer Johns' career development as a postdoctoral DVM, PhD and prepare her for independent research. Dr. Johns is an experienced, board-certified veterinary clinical pathologist with a specific interest in hematologic and hematopoietic alterations in infectious disease and a commitment to advanced biomedical research. Five years of mentored support is requested.

项目概要/摘要： 嗜吞噬细胞无形体是一种蜱传的专性细胞内细菌病原体， 人和动物的粒细胞无形体病。A.嗜吞噬细胞菌主要感染嗜中性粒细胞（PMN）， 破坏正常的PMN凋亡和杀伤机制以促进细菌增殖。相比 内毒素阳性细菌感染，A.嗜吞噬细胞菌感染诱导中性粒细胞减少，尽管增加 骨髓（BM）粒细胞生成。这意味着这种嗜粒细胞的病原体可能从根本上 改变PMN动员的上游调节、PMN从BM释放的下游调节和PMN从BM释放的下游调节。 感染期间PMN的系统性运输和归巢。 中性粒细胞减少和造血系统改变可能是导致A. 嗜吞噬细胞菌感染，包括机会性感染，但机制涉及改变PMN 在A.嗜吞噬细胞菌感染在很大程度上未知。我们的总体假设是A. 嗜吞噬细胞菌感染和病原体复制扰乱正常的PMN运输，并可能最终 促进病原体-PMN相互作用并增强细菌繁殖。预防诱导产生 将研究粒细胞集落刺激因子（G-CSF）和白细胞介素-8（IL-8）作为上游 通过影响中间信号和整合素介导的PMN从BM动员的调节剂 交互.系统性PMN运输和脾归巢将使用复杂的成像来定义 战略布局中性粒细胞运输机制包括趋化梯度和整合素介导的相互作用 将被确定。我们的目标是确定感染诱导的PMN运输机制， 确定它们在先天免疫反应和疾病临床后果中的作用。 KO 1奖将支持Jennifer Johns博士作为博士后DVM，PhD的职业发展 让她做好独立研究的准备约翰斯博士是一位经验丰富的，董事会认证的兽医临床 病理学家，对感染性疾病的血液学和造血改变特别感兴趣， 致力于先进的生物医学研究。要求提供五年的辅导支持。

项目成果

Influence of Genetic Background on Hematologic and Histopathologic Alterations during Acute Granulocytic Anaplasmosis in 129/SvEv and C57BL/6J Mice Lacking Type I and Type II Interferon Signaling.

遗传背景对缺乏 I 型和 II 型干扰素信号传导的 129/SvEv 和 C57BL/6J 小鼠急性粒细胞无形体病期间血液学和组织病理学改变的影响。

• 发表时间: 2017
• 期刊: Comparative medicine
• 影响因子: 0.8
• 作者: Johns,JenniferL;Discipulo,MarielleL;Koehne,AmandaL;Moorhead,KaitlinA;Nagamine,ClaudeM
• 通讯作者: Nagamine,ClaudeM