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Innate immune signaling and stress response

先天免疫信号和应激反应

基本信息

批准号：
10574531
负责人：
Thirumala-Devi Kanneganti
金额：
$ 53.85万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
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：
2016-03-15 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10574531
关键词：
Affect Affinity Chromatography Apoptosis Area Biological Process CASP1 gene Cell Death Cell Survival Cells Cellular Stress Communicable Diseases Cues Cytosol Data Disease Grant Health Homeostasis Human IL18 gene Immune Immune response Immune signaling Immunity Immunology Infection Inflammasome Inflammation Inflammatory Inflammatory Response Influenza A virus Innate Immune Response Interleukin-1 beta Link Malignant Neoplasms Mass Spectrum Analysis Mediating Membrane Molecular Mus Mutation Myeloid Cells Natural Immunity Nature Neurodegenerative Disorders Pathogenicity Pathway interactions Pattern Physiological Play Positioning Attribute Predisposition Production Progress Reports Publications Publishing RNA Regulation Role Science Shapes Signal Pathway Signal Transduction Stress Syndrome Testing Viral Virus Virus Diseases Z-DNA Binding Protein biological adaptation to stress cytokine experimental study helicase human disease in vivo influenza infection influenzavirus innate immune pathways interest membrane assembly microbial new therapeutic target pathogen pathogenic microbe protein complex receptor response sensor stress granule targeted treatment

项目摘要

ABSTRACT Membraneless compartments play a vital role in maintaining cellular and organismal homeostasis by modulating cell survival and cell death. Stress granules, and inflammasome-induced specks are membraneless compartments that provide contrasting cell fate choices to the cells – survival or pyroptosis (programmed cell death) during physiological or virus induced cellular stress. NLRP3, a global sensor of pathogen–associated molecular patterns (PAMPs) and danger–associated molecular patterns (DAMPs), senses cellular perturbations in the cytosol to trigger the assembly of a large caspase-1-activating protein complex termed the NLRP3 inflammasome. Autoproteolytic maturation of caspase-1 due to NLRP3 inflammasome activation leads to pyroptosis, and maturation of pro-inflammatory cytokines interleukin (IL)- 1β and IL-18. Despite the ability of NLRP3 to respond to diverse cues of cellular or virus induced stress, mechanisms controlling the cross-talk between inflammasomes and stress granules remain elusive. In our quest to study this cross-talk, we have identified DDX3X, a stress granule component, as an upstream regulator of NLRP3 inflammasome to canonical and viral triggers. In this R01 renewal, we propose to identify the molecular and cellular mechanisms of DDX3X-mediated NLPR3 inflammasome activation and its modulation by stress signals during inflammation and viral infections. Understanding the cross-talk between cellular stress response molecules and innate immune signaling will lead to novel therapeutic targets for inflammatory and infectious diseases.

文摘