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 这项研究中提出的工作旨在研究奈瑟氏菌对巨噬细胞定植的作用。 淋病(N.G)感染期间对淋病发展的影响。因为N.G是一个高度的人类 适应的病原体，它已经发展出许多机制来避免和主动抑制天生的和适应性的 免疫反应。巨噬细胞大量存在于整个泌尿生殖道粘膜和 约占从这些组织中回收的白细胞总数的10%。因此，N.G很可能 在感染过程中与这些细胞相遇，巨噬细胞在新城疫的发病机制中发挥重要作用。我们 发现N.G在巨噬细胞中定植并建立拓扑上不同的集落。在殖民期间 N.G操纵肌动蛋白细胞骨架，创造一个支持细菌复制的细胞内利基。这 巨噬细胞中N.G持续存在的新模型对淋病症状和预后具有重要意义，因为 体内感染过程中相关的细菌细胞储存库尚未确定。因此，我们 假设N.G定植并改变巨噬细胞的免疫反应以建立持续性 在寄主体内生长。在这项提案的第一个目标中，我们将研究发生在 巨噬细胞在N.G定植过程中感染的细胞和细菌。在第二个目标中，我们将评估 巨噬细胞在新城疫感染小鼠模型中的存在和功能。