Filifactor alocis Pathogenicity Requires TLR2 and the Oral Microbiome

Abstract

Enrichment of the oral microorganism Filifactor alocis is strongly associated with the progression of periodontitis. However, F. alocis is part of a complex dysbiotic microbial community, and the organism’s direct pathogenic potential remains uncharacterized. Using the oral gavage model of experimental periodontitis, we revealed that F. alocis promotes alveolar bone loss, as well as significant overexpression of proinflammatory markers associated with osteoclastogenesis and inflammation in oral tissues. Interestingly, despite colonizing in low abundance, F. alocis infection promoted the perturbation of the homeostatic oral microbial community toward a dysbiotic state. Systemically, high levels of proinflammatory cytokines, chemokines, and antibody titers against F. alocis were detected in the sera of infected animals. Germ-free mice or TLR2-deficient mice did not develop alveolar bone loss when infected with F. alocis, demonstrating that the commensal microbial community and the presence of TLR2 are required for F. alocis to display its pathogenic potential. These findings identify F. alocis as an oral pathogen that can disrupt the homeostatic relationship between the host and the oral microbiome, causing inflammation and alveolar bone resorption. Our findings provide novel insights into the pathogenic potential of F. alocis in periodontitis.