Transcriptome profiling analysis of senescent gingival fibroblasts in response to Fusobacterium nucleatum infection?

Periodontal disease is caused by dental plaque biofilms. Fusobacterium nucleatum is considered an important periodontal pathogen that plays a major role in the development of bacterial complexity in dental plaque biofilms. Human gingival fibroblasts (GFs) act as the first line of defense against oral microorganisms and locally orchestrate immune responses by triggering reactive oxygen species and pro-inflammatory cytokines (IL-6 and IL-8). It is well known that the frequency and severity of periodontal diseases increase in elderly subjects. However, despite several studies about the effects of aging on periodontal diseases, the underlying mechanisms through which aging affects the interaction between F. nucleatum and human GFs remain unclear. To understand the underlying reaction mechanisms, we performed a RNA-Seq analysis on four samples from young GFs (P4) and aged GFs (P22) with or without F. nucleatum infection to investigate the genes affected by infection, aging, and aging-related infection. The results showed that the differentially expressed genes (DEGs) between F. nucleatum-infected and uninfected young GFs were involved in host defense mechanisms (i.e., immune responses and defense responses), whereas DEGs between F. nucleatum-infected and uninfected aged GFs were involved in cell maintenance (i.e., TGF-ß signaling, skeletal development). Intriguingly, most DEGs in F. nucleatum-infected aged GFs were downregulated (85%) and significantly associated with host defense responses such as inflammatory responses, when compared to young GFs. Noticeably, five genes (GADD45b, KLF10, CSRNP1, ID1, and TM4SF1) were upregulated in response to F. nucleatum infection; however, this effect was only seen in aged GFs. Specifically, these genes appear to be interacting with each other in a network associated with free radical scavenging, cell cycle, and cancer; therefore, they could be potential candidates involved in the aged GF’s response to F. nucleatum infection. Further studies are needed to confirm these observations.?