Visualizing invariant NKT cell dynamics following immunization and infection

可视化免疫和感染后不变的 NKT 细胞动态

• 批准号: 8554353
• 负责人: Irah King
• 金额: $ 13.03万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8554353
• 关键词: Address; Agonist; Anti-Bacterial Agents; Antibodies; Antibody Formation; Antigen-Presenting Cells; Antigens; Architecture; B cell differentiation; B-Cell Activation; B-Lymphocytes; Bacteria; Bacterial Infections; Blood; C-Type Lectins; Cells; Cellular Immunity; Communities; Complex; Data; Drug resistance; Event; Exposure to; Frequencies; Future; Generations; Genetic; Gram-Positive Bacteria; Healthcare Systems; Hour; Human; IgG3; Immune; Immune response; Immune system; Immunity; Immunization; Immunoglobulin M; In Situ; Individual; Infection; Infectious Agent; Inflammation; Inflammatory; Interferon Type II; Interferons; Interleukin-4; Interleukins; Knowledge; Leukocytes; Life; Ligands; Lipids; Lung; Lymphocyte; Malpighian corpuscles; Mediating; Methods; Microbe; Morbidity - disease rate; Organ; Peripheral; Phagocytes; Pneumococcal Infections; Pneumonia; Polysaccharides; Population; Production; Publications; Resistance to infection; Rodent; Role; Route; Sentinel; Sepsis; Septicemia; Sinus; Site; Spleen; Staging; Streptococcus pneumoniae; Stromal Cells; Systemic infection; T-Cell Activation; Techniques; Testing; Therapeutic; Vaccine Design; alpha-galactosylceramide; base; cell type; clinically relevant; combat; cytokine; design; extracellular; killer T cell; macrophage; mortality; novel; pathogen; programs; rapid detection; research study; resistant strain; response; sugar; vascular bed

DESCRIPTION (provided by applicant): Surviving systemic infection requires a rapid and vigorous response by innate immune cells residing in the spleen. Indeed, splenectomized humans and rodents are more likely to succumb to systemic bacterial infections than normal individuals. A prominent component of the splenic immune compartment are invariant natural killer T (iNKT) cells, a distinct lineage of innate lymphocytes that recognize self as well as pathogen-derived lipid antigens. Within hours of activation, iNKT cells rapidly exert an effector response that mediates protection against a number of infectious agents including the gram-positive bacteria Streptococcus pneumoniae, the most commonly identified cause of community-acquired pneumonia. Despite their role in antibacterial immunity, the cellular requirements for and functional implications of splenic iNKT cell activation are largely unknown. Combining a novel method to track the endogenous iNKT cell population in situ with various genetic deletion and cell depletion techniques, the studies in this proposal will reveal the localization and antigen-presenting cells required for elaboration of the iNKT cell effector program following pneumococcal infection. Furthermore, we will determine the relevance of iNKT cell activation in terms of the early protective humoral response to S. pneumoniae. These studies will significantly advance our understanding of the complex interplay between cells of the innate immune system and set the stage for future studies investigating the dynamics of iNKT function during infection and inflammation.

描述（由申请人提供）：要生存全身感染，需要脾脏中的先天免疫细胞做出快速而有力的反应。事实上，脾切除的人类和啮齿动物比正常人更容易死于全身细菌感染。脾免疫区室的一个重要组成部分是不变的自然杀伤 T (iNKT) 细胞，这是一种独特的先天淋巴细胞谱系，可识别自身以及病原体衍生的脂质抗原。激活后数小时内，iNKT 细胞迅速发挥效应反应，介导针对多种传染源的保护，包括革兰氏阳性菌肺炎链球菌，这是社区获得性肺炎最常见的病因。尽管它们在抗菌免疫中发挥作用，但脾 iNKT 细胞激活的细胞要求和功能影响在很大程度上尚不清楚。本提案中的研究将一种原位追踪内源性 iNKT 细胞群的新方法与各种基因删除和细胞耗竭技术相结合，将揭示肺炎球菌感染后制定 iNKT 细胞效应程序所需的定位和抗原呈递细胞。此外，我们将确定 iNKT 细胞激活与肺炎链球菌早期保护性体液反应的相关性。这些研究将显着增进我们对先天免疫系统细胞之间复杂相互作用的理解，并为未来研究感染和炎症期间 iNKT 功能动态的研究奠定基础。