Interactions between histophilus somni (haemophilus somnus) and phagocytic cells

睡眠嗜组织菌（Histophilus somni）是一种革兰氏阴性病原菌，能引起牛的多种疾病，包括肺、心脏、关节、脑和生殖道感染。 H.通过抗生素治疗和疫苗接种都可以实现睡眠感染。 然而，鉴于这种疾病综合征的流行在过去十年中一直在增加，显然需要改进控制方法。 生物体致病能力的核心是其逃避宿主先天免疫反应的能力，这是抵抗细菌病原体的第一道防线。 具体来说，H。Somni能够抑制白细胞（包括PMN和巨噬细胞）的抗微生物活性，导致生物体的存活增强和在全身的传播。 我们假设H. Somni产生能够改变宿主先天免疫应答的特异性蛋白质，导致普遍的抑制。 为了验证这一假设，我们将表征细菌产生的新蛋白质，同时使用功能基因组学和传统的蛋白质生物化学技术与牛白细胞孵育。 这些蛋白质将被充分表征，并且分离编码每一种蛋白质的基因并用于构建突变体H。缺乏每一个特定基因的睡眠。 然后测试这些药物干扰PMN功能的能力。 最后，我们将测试这些突变体在牛感染模型中引起疾病的能力。 最终，这将导致疫苗和治疗开发的新靶点的开发。

Histophilus somni is a Gram negative pathogen of cattle capable of causing a variety of diseases, including infections of lung, heart, joints, brain and reproductive tract. The control of H. somni infection has been accomplished through both antibiotic treatment as well as vaccination. However, given that the prevalence of this disease syndrome has been increasing over the past decade, improved control methods are clearly needed. Central to the ability of the organism to cause disease is its capability to evade host innate immune responses, the first line of defense against bacterial pathogens. Specifically, H. somni is able to suppress the antimicrobial activities of leukocytes, including PMNs and macrophages, resulting in enhanced survival of the organism and dissemination throughout the body. It is our hypothesis that H. somni produces specific proteins capable of modifying the host innate immune response, resulting in a general suppression. In order to test this hypothesis, we will characterize new proteins produced by the bacterium while it is incubated with bovine leukocytes using both functional genomic as well as traditional protein biochemistry techniques. These proteins will be fully characterized and the genes coding for each one isolated and used to construct mutant H. somni lacking each specific gene. These will then be tested for their ability to interfere with PMN function. Finally, we will test the ability of these mutants to cause disease in a bovine infection model. Ultimately, this will lead to the development of novel targets for both vaccine and therapeutic development.