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Global changes in human neutrophil transcriptome profile during Filifactor alocis challenge

ABSTRACT: Periodontitis is a multifactorial chronic inflammatory infectious disease with a high prevalence in the adult population in the USA. Until recently, research into periodontitis focused primarily on putative pathogens such as Porphyromonas gingivalis. However, a reappraisal of microbial etiology has marked a turning point in the field due to the development of culture-independent techniques that allow the identification of bacterial species directly from nucleic acids. Filifactor alocis, a Gram positive anaerobic oral bacterium, has emerged as an important periodontal pathogen. Neutrophils are recruited in high numbers to the gingival tissue, where they are linked with protection against periodontal disease. However, periodontal pathogens evolved different strategies to resist neutrophil microbicidal mechanisms while propagating inflammation, which affords a source of nutrients. The goal of this study was to determine the global changes in human neutrophil gene expression induced by F. alocis challenge. RNA-sequencing analysis shows that F. alocis-challenge alters human neutrophil transcriptome including expression of genes associated with regulation of Toll-Like Receptor signaling pathway, MAPK signaling pathway, apoptosis, cytokines and chemokines, among other neutrophil effector functions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137351 | GEO | 2020/04/06

REPOSITORIES: GEO

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Project description:Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation.

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Global changes in human neutrophil transcriptome profile during Filifactor alocis challenge

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