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Global analysis of circuitry governing fungal activation of host inflammation

控制宿主炎症真菌激活的电路的整体分析

基本信息

批准号：
10461630
负责人：
Teresa R. OMeara
金额：
$ 3.51万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10461630
关键词：
Address Antifungal Agents Apoptosis Biological Candida albicans Candidate Disease Gene Caspase Cell Death Cell Survival Cell Wall Cells Collection Cryptococcus neoformans Cytolysis Development Drug resistance Environment Enzymes Exposure to Fungal Genes Gene Expression Genes Genetic Transcription Goals Health Human Immune Immune response Immunocompromised Host Individual Infection Inflammasome Inflammation Inflammatory Innate Immune System Integration Host Factors Interleukin-1 beta Invaded Macrophage Activation Maps Mediating Medical Mus Mycoses Pathway interactions Phagocytes Phagocytosis Phagosomes Pharmaceutical Preparations Phenotype Population Portraits Process Proliferating Research Resistance development Resolution Rest Signal Transduction Therapeutic Therapeutic Intervention Toxic effect Work drug development functional genomics fungus gene function genome-wide human disease interdisciplinary approach knock-down macrophage microbial microorganism mutant neutrophil new therapeutic target novel therapeutics pathogen pathogenic fungus programs response screening

项目摘要

Project Summary / Abstract Fungal pathogens take a devastating toll on human health worldwide, and fungal infections are on the rise due to the growing population of immunocompromised individuals. Treating fungal infections is extremely difficult, as fungi are closely related to humans and there are very few drugs that kill the fungus without host toxicity. With the emergence of drug resistance, the development of new therapeutics is now crucial. To address this unmet medical need and identify new targets for drug development, it is critical to uncover mechanisms that enable these pathogens to cause human disease. I have developed a powerful approach to study the front line of human defense against these fungal pathogens. Host innate immune cells recognize and engulf the invading pathogens, but the fungal cells are able to adapt and trigger immune cell death. I recently discovered that this immune cell death requires fungal cell wall remodeling and the NLRP3 inflammasome. However, the specific trigger and mechanisms involved remain enigmatic. Here, I propose an interdisciplinary approach to examine mechanisms by which fungi are able to induce host cell death, and the host pathways that are required for responding to the invading pathogen. Our global analyses of fungal gene expression, gene function and host immune responses will provide a high-resolution portrait of this host-pathogen interface, and reveal new targets for therapeutics to save human lives.

项目摘要/摘要