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Equipment Supplement request for a BD LSR Fortessa Flow Cytometer

BD LSR Fortessa 流式细胞仪的设备补充请求

基本信息

批准号：
9275190
负责人：
EDWARD R SHERWOOD
金额：
$ 12.74万
依托单位：
EAST TENNESSEE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9275190
关键词：
Accounting Acute Address Adult Respiratory Distress Syndrome Agonist Anti-Inflammatory Agents Anti-inflammatory Antibiotic Resistance Bacterial Model Burn injury Candida albicans Cause of Death Cessation of life Complex Cost of Illness Critical Illness Data Disease Disease Management Equipment Event FDA approved Failure Functional disorder Glucans Grant Health Hospitals Human Immune Immune System Diseases Immune response Immune system Immunity Immunologics Immunosuppression Immunosuppressive Agents Incidence Infection Inflammation Inflammatory Response Institution Intensive Care Units Lead Life Ligands Ligation Literature Mediating Metabolic Modeling Molecular Molecular Structure Morbidity - disease rate Multiple Organ Failure Mus Natural Products Neurologic Opportunistic Infections Organ Organ failure Outcome Patients Pattern recognition receptor Pharmaceutical Preparations Phenotype Physically Handicapped Physiological Population Predisposition Prevention Primary Infection Procedures Prophylactic treatment Publishing Puncture procedure Race Recurrence Research Resistance Respiratory distress Science Secondary to Sepsis Sepsis Syndrome Septic Shock Shock Signal Pathway Signal Transduction TLR2 gene Testing Training Treatment Efficacy United States United States National Institutes of Health Vulnerable Populations aging population antimicrobial base clinically relevant cognitive disability dectin 1 disability drug candidate effective therapy experience high risk immune function improved innate immune function macrophage monocyte mortality mouse model novel novel strategies novel therapeutics pathogen physical state prevent prophylactic research study response secondary infection septic small molecule trend wound

项目摘要

DESCRIPTION (provided by applicant): This application is submitted under the NIH multiple PI initiative (http://grants.nih.gov/grants/guide/notice- files/NOT-OD-11-118.html). Drs. Ed Sherwood and David Williams with serve as the PIs. The multiple PI strategy is advantageous because it enables a "team science" approach that will draw equally on the expertise and experience of both of the PIs as well as their respective institutions. The critically ill patient frequently develops a complex disease spectrum that may include acute respiratory distress syndrome, systemic inflammatory response syndrome, sepsis syndrome, septic shock and/or multiple organ dysfunction syndrome. In the United States ~951,000 patients/year develop sepsis with approximately half of these patients in the ICU. The overall mortality rate is 28.6%. Those patients that survive the initial septic event may ultimately succumb to widespread organ dysfunction that can be either acute, due to hyper-inflammatory responses, or more prolonged due to immune dysfunction. It is well accepted that sepsis causes suppression of the immune system and that sepsis-induced immunoparalysis predisposes the critically ill patient to secondary infections. Attempts at developing effective therapies to prevent or treat sepsis and its associated immunosuppression have proven to be exceedingly difficult. In fact, no drugs are currently approved by the FDA for the management of sepsis. Recent data have provided compelling evidence that the innate immune system can be "trained" to respond more rapidly and effectively to pathogens following treatment with Dectin-1 agonists. We have successfully synthesized Dectin-1 ligands that increase resistance to sepsis. In this application, we propose the novel concept that it may be possible to "train" the compromised immune system with synthetic Dectin-1 ligands, such that an effective response can be mounted to existing and/or subsequent infections. We hypothesize that "immunologic training and metabolic reprogramming will decrease septic morbidity and mortality in clinically relevant models of sepsis and augment host immunity in vulnerable populations". To critically evaluate this hypothesis, we propose the following specific aims. Aim 1. Determine the effects of immune training on sequelae and outcomes in CLP-induced polymicrobial sepsis. This aim will define the efficacy of immune training in murine model of polymicrobial sepsis. Specifically, this aim wil determine if synthetic Dectin-1 agonists can "train" the immune system to prevent and/or treat polymicrobial sepsis. Aim 2. Determine the effect of immune training on sequelae and outcomes in a clinically relevant model of post-burn immunosuppression. This aim will establish whether training will improve survival in clinically relevant model of post-burn immunosuppression. Aim 3. Establish the impact of training on innate immune parameters in sepsis. This aim will define the alterations in innate immune function by which training augments the host response to infection. Aim 4. Define the mechanisms by which synthetic Dectin-1 ligands induce trained immunity. This aim will define the specific signaling alterations by which immune training enhances antimicrobial responses in populations that are at high risk of developing infections.