Schistosome antigen induced modulation of metabolism

血吸虫抗原诱导的代谢调节

• 批准号: 10304040
• 负责人: Keke Celeste Fairfax
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304040
• 关键词: Animal Model; Antiatherogenic; Antidiabetic Drugs; Antigens; Apolipoprotein E; Area; Asthma; Atherosclerosis; Biological Assay; Blood group antigen S; Bone Marrow; Cardiovascular Diseases; Cardiovascular system; Chronic; Data; Development; Diabetes Mellitus; Disease; Exposure to; Foundations; Fractionation; Future; Gene Expression Profile; Genus Hippocampus; Glucose Intolerance; Goals; Helminth Antigens; Helminths; High Fat Diet; Immunologics; In Vitro; Individual; Infection; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Insulin Resistance; Interleukin-4; Knowledge; Laboratories; Legal patent; Lipids; Literature; Mature Bone; Metabolic; Metabolic Diseases; Metabolic syndrome; Metabolism; Mitochondria; Modeling; Morbidity - disease rate; Mus; Myelogenous; Myeloid Cells; Obesity; Outcome Measure; Parasites; Pathology; Pathway interactions; Phenotype; Population; Prediabetes syndrome; Proteins; Proteomics; Recording of previous events; Regulation; Research; Respiration; Risk; Risk Factors; Role; Schistosoma; Schistosoma mansoni; Schistosoma mansonii infection; Testing; base; chronic inflammatory disease; cytokine; diabetic; diabetic patient; egg; experimental study; extracellular; helminth infection; immunoregulation; in vivo; innovation; lipidome; macrophage; male; metabolic phenotype; metabolic profile; mitochondrial metabolism; mortality; mouse model; new therapeutic target; non-diabetic; novel; programs; protective effect; screening; success; therapy development; transcriptome

Project Summary Globally, parasitic helminth infections inversely correlate with metabolic diseases, such as diabetes, atherosclerosis, and obesity, but the parasite factors that are capable of modulating metabolic disease are currently unknown. Diabetic patients are twice as likely as non-diabetic individuals to develop cardiovascular disease, with more than 65% of diabetic patients dying from cardiovascular complications, thus there is a critical need for identifying novel compounds capable of modulating insulin resistance, obesity, and atherosclerosis in this population. Recent evidence has suggested that inflammation driven by macrophages is associated with both obesity and insulin resistance, while atherosclerosis is accepted to be driven by lipid- dependent chronic myeloid inflammation. Our laboratory has recently identified that Schistosoma mansoni infection modulates the metabolic transcriptome of the myeloid lineage, and that this modulation is correlated with protection from the development of insulin resistance, diabetes, and atherosclerosis in the ApoE-/- high fat diet mouse model. Our lab and others have established that in vivo metabolic protection is dependent on exposure to egg antigens, but the antigens sufficient to confer protection are unknown. To fill these current knowledge gaps, we propose to perform proteomic analysis and screening to identify the antigens sufficient to modulate macrophage metabolism. We will first 1) identify pools of antigens sufficient to modulate mature bone marrow derived macrophage metabolism, and then 2) determine the subset of antigens sufficient to program bone marrow precursors to generate immunomodulated macrophages in vivo. The data generated from these studies will lay the foundation for future studies on understanding the role of helminth induced macrophages in the long-term regulation of whole-body metabolism.

项目总结