Interactions between histophilus somni (haemophilus somnus) and phagocytic cells

索姆尼组织杆菌是一种革兰氏阴性病原体，可引起多种疾病，包括肺、心脏、关节、脑和生殖道感染。通过抗生素治疗和接种疫苗实现了对索姆尼嗜血杆菌感染的控制。然而，鉴于这种疾病综合征的流行率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它逃避宿主先天免疫反应的能力，这是抵御细菌病原体的第一道防线。具体地说，H.Somni能够抑制包括PMN和巨噬细胞在内的白细胞的抗菌活性，从而提高生物的存活率并在全身传播。我们的假设是，H.Somni产生特定的蛋白质，能够修改宿主的先天性免疫反应，导致普遍的抑制。为了验证这一假设，我们将使用功能基因组和传统的蛋白质生物化学技术来表征细菌与牛白细胞孵育时产生的新蛋白质。这些蛋白质将被充分鉴定，每个蛋白质的编码基因将被分离出来，并用于构建缺失每个特定基因的突变索姆尼杆菌。然后将测试这些细胞干扰PMN功能的能力。最后，我们将在牛感染模型中测试这些突变体的致病能力。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.