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Cytosolic Immune Surveillance During Bacterial Infections

细菌感染期间的细胞质免疫监视

基本信息

批准号：
10625492
负责人：
Vijay Rathinam
金额：
$ 41万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
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：
2016-03-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10625492
关键词：
Address Anti-Bacterial Agents Autoimmunity Bacteria Bacterial Infections Binding Binding Proteins Biological Assay Burkholderia CASP1 gene Carbohydrates Caspase Cell Death Cells Co-Immunoprecipitations Communicable Diseases Confocal Microscopy Coupled Cytosol DNA Disease Endosomes Event Excision Family Francisella Galactose Binding Lectin Galectin 3 Glycoproteins Gram-Negative Bacteria Homeostasis Host Defense Human IL18 gene Image Immune Immunologic Surveillance Impairment In Vitro Infection Inflammasome Inflammatory Inflammatory Response Interleukin-1 beta Knockout Mice Knowledge Label Licensing Life Link Lipopolysaccharides Lytic Macromolecular Complexes Malignant Neoplasms Mass Spectrum Analysis Mediating Membrane Modeling Molecular Monitor Mus Pathologic Processes Pathway interactions Pattern Peptide Hydrolases Physiological Processes Play Polysaccharides Process Proteins Regulation Role Salmonella Sepsis Series Shapes Side Signal Transduction Specificity Translational Activation Trauma VDAC1 gene Vacuole Vesicle Virus Diseases antimicrobial beta-galactoside carbohydrate binding protein carbohydrate receptor cell type endosome membrane guanylate immunoregulation in vivo insight microbial mutant pathogen pathogenic Escherichia coli repaired response sensor ultra high resolution

项目摘要

Inflammasomes sense an array of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) generated during infection and trauma and represent the first line of defense against infections. In the canonical form, inflammasomes consist of a sensor protein that recognizes PAMPs, an adaptor molecule ASC, and an effector protease, caspase-1. In the noncanonical form, inflammatory caspases related to caspase-1, namely caspase-11 and caspase-4, directly sense cytosolic lipopolysaccharide (LPS) from Gram- negative bacteria and their outer membrane vesicle. Inflammasome signaling culminates in the post-translational activation of IL-1β, IL-18, gasdermin D (a pore-forming protein), and pyroptosis, a lytic and inflammatory form of cell death, and the simultaneous release of DAMPs. Despite the profound implications of inflammasome responses in infections, cancer, and autoimmunity, the regulatory modules that fine-tune the initiation and termination of inflammasome signaling remain mostly unknown. This proposal seeks to comprehensively address this critical knowledge gap in three specific aims by focusing on galectins, a family of β-galactoside-binding proteins. Owing to their capacity to bind to N- or O-glycan termini of various glycoproteins and regulate their membrane localization and signal transduction, galectins have diverse functions in various physiological and pathological processes. Aims 1 and 2 of the proposal will investigate galectins' role in noncanonical inflammasome signaling in murine and human cells and in vivo. Aim 3 will explore how galectins control canonical inflammasome signaling in vitro and in vivo. In summary, the findings from this project would reveal new players in inflammasome signaling with significant implications for human infectious diseases and sepsis.

炎性小体感知一系列病原体相关分子模式（PAMPs）和

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intracellular immune sensing promotes inflammation via gasdermin D-driven release of a lectin alarmin.

DOI：
10.1038/s41590-020-00844-7
发表时间：
2021-03
期刊：
Nature immunology
影响因子：
30.5
作者：
Russo AJ;Vasudevan SO;Méndez-Huergo SP;Kumari P;Menoret A;Duduskar S;Wang C;Pérez Sáez JM;Fettis MM;Li C;Liu R;Wanchoo A;Chandiran K;Ruan J;Vanaja SK;Bauer M;Sponholz C;Hudalla GA;Vella AT;Zhou B;Deshmukh SD;Rabinovich GA;Rathinam VA
通讯作者：
Rathinam VA

Bacterial Outer Membrane Vesicles Mediate Cytosolic Localization of LPS and Caspase-11 Activation.