Filifactor alocis FtxA blocks inflammation and apoptosis pathways in monocytic cells

Filifactor alocis is an emerging oral pathogen, and approximately 50% of known F. alocis strains encode and express a Repeats-in-Toxin (RTX) protein, FtxA. FtxA appears to be associated with both progress and severity of periodontal disease. Mechanisms are not yet known but could be linked to increased loads of F. alocis in ftxA-positive strains. Here, we investigated mechanistic correlations based on FtxA-activity, as present in F. alocis cells and extracellular vesicles and as a recombinant protein, exploiting THP-1 macrophage-like cells. For this, we used the ftxA-expressing strain, ATCC 35896 (ftxA ⁺), and F. alocis 148B-17U (ftxA ^-), which naturally lacks the ftxA gene. Using RNA sequencing analysis (RNA-Seq) and cytokine array analysis, we have pinpointed a role of FtxA in shifting host response toward immunosuppression, also inhibiting apoptosis and immune cell recruitment, and with a potential role in downregulating mitochondrial and oxidative phosphorylation pathways. Such role(s) could provide a plausible explanation why FtxA is associated with progress and severity of periodontal disease, and further studies on FtxA-host cell interactions might reveal novel potential therapeutic targets.