Contribution of macrophages to Neisseria gonorrhoeae pathogenesis

巨噬细胞对淋病奈瑟菌发病机制的贡献

• 批准号: 10569059
• 负责人: Ana-Maria Dragoi
• 金额: $ 21.79万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569059
• 关键词: Actins; Adherence; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Anus; Apoptosis; Bacteria; Betaproteobacteria; Bioinformatics; Cells; Cephalosporin Resistance; Cicatrix; Coupled; Cytoskeleton; Development; Disease; Environment; Epithelium; Etiology; Frequencies; Genetic Materials; Genetic Transcription; Genital; Genitalia; Genitourinary system; Gonorrhea; Growth; Half-Life; Human; Immune response; Immune system; Immunology; Immunophenotyping; Incidence; Infection; Innate Immune Response; Innate Immune System; Invaded; Investigation; Left; Lysosomes; Macrophage; Mammalian Oviducts; Mediating; Modeling; Molecular; Morbidity - disease rate; Mucous Membrane; Nasopharynx; Neisseria gonorrhoeae; Outcome; Pathogenesis; Pathologic Processes; Pathology; Pathway interactions; Pelvic Inflammatory Disease; Phagocytes; Phase; Pilum; Play; Polymers; Process; Protein Family; Proteins; Public Health; Role; Sexually Transmitted Diseases; Site; Testing; Therapeutic; Therapeutic Intervention; Tissues; VDAC1 gene; Vaccines; White Blood Cell Count procedure; Woman; Work; adaptive immune response; bacterial resistance; carcinoembryonic antigen-related cell adhesion molecules; design; extracellular; fluoroquinolone resistance; in vivo; lipooligosaccharide; major outer membrane protein; mortality; mouse model; neutrophil; new therapeutic target; novel therapeutics; pathogen; polymerization; reproductive tract; symptomatology; transcriptional reprogramming

Project 2 - ABSTRACT The work proposed in this study seeks to investigate the role of macrophages colonization by Neisseria gonorrhoeae (N.g) during infection and the impact on gonorrhea development. Because N.g is a highly human adapted pathogen, it has developed numerous mechanisms to avoid and actively suppress innate and adaptive immune responses. Macrophages are present in significant numbers throughout the genitourinary mucosae and represent about 10% of total number of leukocytes recovered from these tissues. Thus, it’s likely that N.g encounters these cells during infection and that macrophages play an important role in N.g pathogenesis. We uncovered that N.g colonizes and establishes topologically distinct colonies in macrophages. During colonization N.g manipulates the actin cytoskeleton to create an intracellular niche supportive of bacterial replication. This new model of N.g persistence in macrophages is significant for gonorrhea symptomatology and outcome, since the relevant cellular reservoir of bacteria during in vivo infections has yet to be identified. Therefore, we hypothesize that N.g colonizes and alters the macrophages immune response in order to establish persistent growth within its host. In the first aim of this proposal we will investigate the transcriptional changes that occur in the infected cell and the bacterium during N.g colonization of macrophages. In the second aim we will assess the presence and the function of macrophages in a mouse model of N.g infection.

项目 2 - 摘要 本研究提出的工作旨在研究奈瑟菌巨噬细胞定植的作用 淋病 (N.g) 感染期间及其对淋病发展的影响 因为 N.g 是一种高度人性化的病毒。 它已经适应了病原体，它已经发展出许多机制来避免和主动抑制先天性和适应性 巨噬细胞在整个泌尿生殖系统粘膜中大量存在。 约占从这些组织中回收的白细胞总数的 10% 因此，N.g. 在感染过程中会遇到这些细胞，巨噬细胞在 N.g 发病机制中发挥重要作用。 发现 N.g 在定植期间在巨噬细胞中定殖并建立拓扑不同的集落。 N.g 操纵肌动蛋白细胞骨架来创建支持细菌复制的细胞内生态位。 N.g 在巨噬细胞中持续存在的新模型对于淋病症状和结果具有重要意义，因为 体内感染过程中相关的细菌细胞库尚未确定。 促进 N.g 定植并改变巨噬细胞免疫反应，以建立持久的免疫反应 在该提案的第一个目标中，我们将研究发生在其宿主内的转录变化。 在第二个目标中，我们将评估巨噬细胞 N.g 定植期间的受感染细胞和细菌。 N.g 感染小鼠模型中巨噬细胞的存在和功能。