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Inflammasome activation by Salmonella typhimurium biofilms

鼠伤寒沙门氏菌生物膜激活炎症小体

基本信息

批准号：
9282745
负责人：
Cagla Tukel
金额：
$ 19.5万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
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：
2016-06-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9282745
关键词：
Acute Amyloid Amyloid Proteins Amyloid beta-Protein Amyloid fibers Apoptosis Bacteria Bacterial Infections CASP1 gene Caspase Cell Death Cells Data Development Disease Enzymes Epithelial Epithelial Cells Extracellular Matrix Fiber Flagellin Generations Goals Human Immune Targeting Immune response Immune system Immunologic Surveillance Infection Inflammasome Inflammatory Innate Immune Response Interleukin-1 Interleukin-1 beta Interleukin-17 Interleukin-18 Intestines Knowledge Microbial Biofilms Morbidity - disease rate Multiprotein Complexes Mus Pathogenesis Pathogenicity Pattern recognition receptor Play Production Proteins Role Salmonella Salmonella enterica Salmonella infections Salmonella typhimurium Serum amyloid A protein Signal Transduction Structure Systemic infection TLR2 gene Testing United States beta pleated sheet cytokine foodborne host-microbe interactions innovation islet amyloid polypeptide killings macrophage mortality mutant novel novel therapeutic intervention protein structure public health relevance receptor response

项目摘要

Summary Activation of cytosolic activation of Nod like receptors (NLRs) induces the assembly of inflammasomes, which are cytosolic multiprotein complexes that activate inflammatory caspases (caspase-1 and -11). These caspases promote the cleavage of pro-IL-1 and pro- IL-18 to active IL-1 and IL-18, triggering also pyroptosis, an inflammatory cell death that kills the infected cell. IL-1 is a key cytokine that has been implicated in the pathogenesis of several inflammatory diseases as well as bacterial infections including Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. NLRP3 is the best-characterized inflammasome, which can be activated with a wide range of danger signals and uses apoptosis-associated speck-like protein containing a CARD (ASC) as an adaptor molecule. Nonetheless, the molecule that trigger NLRP3 assembly during S. Typhimurium infection is not known. Amyloid proteins, produced both by bacteria and humans, are characterized by their conserved cross--sheet quaternary structure. Amyloid fibers are an important extracellular matrix component of biofilms formed by diverse groups of bacteria. Intriguingly, human amyloid-, islet amyloid polypeptide and serum amyloid A (SAA) have all been demonstrated to activate the NLRP3 inflammasome resulting in the production of IL-1 . Our long-range goal is to elucidate the role of bacterial amyloids in microbe-host interactions. Amyloid fibers produced in the biofilms of S. Typhimurium are termed curli and have been shown to be expressed during infection. The objective of this application is to determine whether bacterial amyloid curli would trigger IL-1 and IL-18 production through NLRP3 activation during S. Typhimurium infection.

总结