Mechanisms by which M. tuberculosis 13KDa lectin modulates human immune responses

结核分枝杆菌 13KDa 凝集素调节人体免疫反应的机制

• 批准号: 8311544
• 负责人: Andre Bafica
• 金额: $ 5.31万
• 依托单位: FEDERAL UNIVERSITY OF SANTA CATARINA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311544
• 关键词: Agonist; Antibiotic Therapy; Antigen-Presenting Cells; Antitubercular Agents; Bacteria; Binding; Biochemical; Bioinformatics; Biological Markers; Blocking Antibodies; Brazil; C Type Lectin Receptors; C-Type Lectins; CD209 gene; CD80 gene; Cell Communication; Cell Culture Techniques; Cell Line; Cell physiology; Cells; Cities; Coculture Techniques; Communicable Diseases; Confocal Microscopy; Cytokine Gene; Cytometry; Data; Data Analyses; Databases; Dendritic Cells; Development; Diagnostic; Disease; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Exposure to; Family; Flow Cytometry; Gene Expression; Genes; Genus Mycobacterium; Goals; Green Fluorescent Proteins; Health; Host resistance; Human; Immune response; Immune system; Immunity; Immunoglobulin G; Immunologic Receptors; Immunotherapy; In Vitro; Infection; Inflammation Mediators; Inflammatory; Interferon Type II; Interleukin-10; Interleukin-12; Interleukin-17; Interleukin-6; Knowledge; Lectin; Lung diseases; MHC Class II Genes; Macrophage-1 Antigen; Measures; Membrane; Modeling; Monoclonal Antibodies; Mus; Mycobacterium smegmatis; Mycobacterium tuberculosis; Outcome; Outcome Study; Pathogenesis; Pathway interactions; Patient Monitoring; Patients; Pattern; Peripheral Blood Mononuclear Cell; Phagocytosis; Play; Preparation; Process; Production; Protein Binding Domain; Proteins; Publishing; Reagent; Recombinants; Research; Ricin; Role; Screening procedure; Serum; Surface; System; T-Cell Proliferation; T-Lymphocyte; TLR2 gene; TLR3 gene; TLR4 gene; TLR7 gene; TNF gene; TNFRSF5 gene; Testing; Time; Toll-like receptors; Tuberculosis; Virulence; Work; base; chemotherapy; cohort; cytokine; dectin 1; glucan phosphate; immunoprophylaxis; improved; in vivo; interest; interleukin-23; laminaran; macrophage; monocyte; mycobacterial; neutralizing antibody; novel; pathogen; protein protein interaction; receptor; receptor expression; research study; response; stem; sugar; tool; tuberculosis treatment; uptake

Mechanisms by which M. tuberculosis 13 kDa lectin modulates human immune responses Project Summary Study of novel proteins from Mycobacterium tuberculosis may be a critical step for improving diagnostic tools, therapies and immunoprophylaxis against tuberculosis (TB), one of the most prevalent infectious diseases wordwide. We have identified a 13 KDa ricin-like lectin from M. tuberculosis that was found to agglutinate red blood cells and induce cytokine expression by macrophages. Moreover, serum from active tuberculosis patients contained high levels of IgG against this lectin. In the present proposal, we aim to characterize the role of 13 KDa Mtb lectin on human immune responses. The specific aims of the study are to 1) characterize the innate immune response profile elicited by the 13 KDa Mtb lectin; 2) determine innate receptor(s) expressed on human APC involved in the recognition of 13 KDa Mtb lectin; 3) investigate the role of 13 KDa Mtb lectin in the infection/phagocytosis process of M. tuberculosis by human APC and 4) examine specific humoral and cellular immune responses against 13 KDa Mtb lectin in TB patients before and after antibiotic treatment. Our long-term goal is to determine whether 13 KDa Mtb ricin-like lectin plays a role in regulating human immune responses to TB focusing on it possible activity in controlling APC function. These studies could be important in revealing a new target for immunotherapy of tuberculosis.

M.结核13 kDa凝集素调节人 免疫应答 项目摘要 研究结核分枝杆菌的新蛋白质可能是治疗结核病的关键步骤。 改进结核病的诊断工具、疗法和免疫预防， 世界范围内最流行的传染病之一。我们发现了一个13 KDa的 蓖麻毒素样凝集素;结核病，被发现凝集红细胞， 诱导巨噬细胞表达细胞因子。此外，活动性肺结核的血清 患者含有高水平的抗这种凝集素的IgG。在本提案中，我们的目标是 以表征13 KDa Mtb凝集素对人免疫应答的作用。具体 本研究的目的是：1）表征引起的先天免疫应答谱 通过13 KDa Mtb凝集素; 2）确定在人类细胞上表达的先天性受体 APC参与13 KDa Mtb凝集素的识别; 3）研究13 KDa Mtb凝集素在APC识别Mtb凝集素中的作用。 KDa Mtb凝集素在M.人类结核病 APC和4）检查针对13种抗原的特异性体液和细胞免疫应答 结核病患者抗生素治疗前后KDa Mtb凝集素的变化我们的长期 目的是确定13 KDa Mtb蓖麻毒素样凝集素是否在调节人类 针对TB的免疫应答集中于其在控制APC功能中的可能活性。 这些研究对于揭示免疫治疗的新靶点可能很重要。 结核