Distinct Polarization of Human Macrophages in Response to Infection with the Periodontitis-Associated Bacteria Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia

Periodontal health and disease are shaped by a dynamic interaction between the subgingival microbiome and the host immune system, in which gingival macrophages contribute to tissue homeostasis, disease progression, and inflammation resolution. Here, we investigated how three periodontitis-associated bacteria, Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia, shape the polarization of human macrophages in vitro. THP-1 monocytes were differentiated into unpolarized M0 macrophages, or polarized toward the M1 or M2 phenotype, and infected with each bacterium at different multiplicities of infection. Polarization was assessed from the surface expression of CD80 (M1) and CD209 (M2) and from pro- and anti-inflammatory cytokine production, measured by a multiplex assay. The response to P. gingivalis differed strikingly from the two other species. Porphyromonas gingivalis suppressed both M1 and M2 polarization and reduced the levels of several pro- and anti-inflammatory cytokines. In contrast, F. nucleatum and T. forsythia enhanced CD80 expression and pro-inflammatory cytokine production in M1 macrophages and modestly increased pro-inflammatory mediators in M2 macrophages. These findings point to a distinct role for P. gingivalis as a keystone pathogen that subverts the innate immune response, and for F. nucleatum and T. forsythia as periodontal pathobionts.