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Filifactor alocis interactions with neutrophils

Filifactor alocis 与中性粒细胞的相互作用

基本信息

批准号：
10458581
负责人：
Silvia M Uriarte
金额：
$ 45.41万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458581
关键词：
Address Adult Affect Alveolar Bone Loss Anaerobic Bacteria Apoptosis Apoptotic Bacteria Biology Bone Marrow Cells Chemotaxis Communities Complex Cytoplasmic Granules Data Development Disease Disease Progression Etiology Exocytosis Experimental Models Focal Infection Foundations Fusobacterium nucleatum Gene Expression Generations Gingiva Goals Health Status High-Throughput Nucleotide Sequencing Human Immune Immune response In Vitro Indigenous Infection Inflammation Inflammatory Inflammatory Response Intention Knowledge Laboratories Leukocytes Longevity Mediating Molecular Mus NF-kappa B Oral Oral health Organism Pathogenesis Pathogenicity Pathology Periodontal Diseases Periodontal Pocket Periodontitis Phagocytes Phagosomes Play Porphyromonas gingivalis Process Proteins Publishing Reactive Oxygen Species Regulation Research Research Personnel Rod Role Secure Signal Pathway Signal Transduction Site Stimulus TLR2 gene Techniques Testing Tissues United States Virulence Work antimicrobial bactericide bone loss chronic inflammatory disease combat cytokine defined contribution density dysbiosis extracellular host-microbe interactions in vivo in vivo Model innovation microbial microbial community microbial composition microbicide microbiota neutrophil novel therapeutic intervention oral bacteria oral biofilm oral pathogen pathogenic bacteria periodontopathogen preservation prevent programs recruit response trafficking transcriptome transcriptome sequencing

项目摘要

Abstract Periodontitis is one of the six most common chronic inflammatory diseases affecting ~ 50% of the adults in the USA. The etiology of periodontitis is strongly associated with changes in both the microbial composition and density of an indigenous symbiotic community to a more diverse dysbiotic microbial community. High-throughput sequencing techniques applied to characterize the composition of the periodontal microbiota obtained from disease sites, revealed the presence of high number of newly appreciated oral pathogens. Among these is the Gram-positive anaerobic rod Filifactor alocis, present in high numbers in the oral biofilm of periodontal disease sites compared to healthy sites. The challenge now is to determine the potential pathogenicity, virulence mechanisms and possible immune subversion arsenal of F. alocis. The response that the host mounts to the bacterial challenge plays a major role in disease progression. Neutrophils are the primary leukocyte recruited to the subgingival crevice and their interaction with the microbial community is a key determinant of oral health status. Understanding how the host responds to the different microbial challenges will increase our knowledge of the disease process. The current proposal will test the hypothesis that F. alocis undermines neutrophil effector functions to promote its survival. We will test our hypothesis by the following specific aims: Aim 1: To define F. alocis regulation of neutrophil vesicular trafficking to evade killing and promote bacteria colonization and bone loss. The goal of this aim will be to test the hypothesis that F. alocis manipulates neutrophil signaling pathways to uncouple the bactericidal activity from the inflammatory response to successfully evade killing. Aim 2: To characterize F. alocis ability to modulate apoptosis in human neutrophils. The goal of this aim will be to test the hypothesis that F. alocis modulates neutrophils apoptotic program as a virulence strategy to preserve an intracellular niche within the neutrophil phagosome. The current project is a collaborative effort from an investigator who is an expert in the field of neutrophil biology and inflammation and its interactions with emerging oral pathogens (Dr. Uriarte) and an expert in the field of oral pathogens and host cell responses using in vivo models of periodontitis (Dr. Lamont). The proposed collaborative efforts offer an innovative and strong framework to characterize the pathogenic potential of F. alocis. In addition, the data generated from this application will fill a significant gap in our knowledge and lay the foundation for development of new therapeutic approaches to combat periodontitis.

摘要