Interaction Of Pathogenic Bacteria With Leukocytes

致病菌与白细胞的相互作用

• 批准号: 6546348
• 负责人: FRANK R DELEO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6546348
• 关键词: CD antigens; Staphylococcus aureus; Streptococcus pyogenes; antigen receptors; apoptosis; bacterial proteins; bactericidal immunity; gene induction /repression; host organism interaction; human tissue; immunogenetics; microarray technology; neutrophil; oligonucleotides; phagocytosis; proteomics

Project Goals and Objectives: Specific projects will 1) identify and characterize specific mechanisms used by pathogenic bacteria to evade or subvert normal phagocyte responses and therefore cause disease, and 2) investigate human phagocyte response mechanisms to pathogenic bacteria. Research Accomplishments: 1) We have determined that Group A Streptococcus secretes a homologue of human CD11b that blocks innate and acquired immune function. This represents a novel mechanism by which Group A Streptococcus can survive during the course of human infection. 2)We used human oligonucleotide microarrays (Affymetrix GeneChip) to determine global gene expression profiles in human PMNs during receptor-mediated phagocytosis. We discovered that gene transcription following phagocytosis serves mainly to determine PMN fate. We identified entire apoptotic pathways (>100 genes) for activated human PMNs and for those undergoing spontaneous apoptosis. These studies will be used as a springboard for studies with human pathogens.

项目目的和目标：具体项目将 1) 识别和表征病原菌用于逃避或破坏正常吞噬细胞反应并因此引起疾病的特定机制，2) 研究人类吞噬细胞对病原菌的反应机制。研究成果： 1) 我们确定A组链球菌分泌人类CD11b的同源物，可阻断先天性和后天性免疫功能。这代表了 A 族链球菌在人类感染过程中得以存活的新机制。 2)我们使用人类寡核苷酸微阵列（Affymetrix GeneChip）来确定受体介导的吞噬作用期间人类中性粒细胞中的全局基因表达谱。我们发现吞噬作用后的基因转录主要决定中性粒细胞的命运。我们确定了激活的人类中性粒细胞和那些经历自发性细胞凋亡的细胞的完整细胞凋亡途径（> 100 个基因）。这些研究将用作人类病原体研究的跳板。