Repeated exposures to Porphyromonas gingivalis alter dendritic cell function resulting in pathogenic immunity

Objectives: Repetitive exposures to periopathogen are regularly employed to induce experimental periodontitis. Nevertheless, it is unclear what impact such recurring infections have on the immune system, driving to the development of destructive response. Dendritic cells (DCs) are the key cells orchestrating adaptive immunity, and are of major importance in controlling the transition of immunity from protective to destructive one. We aim to elucidate the mechanisms involved in this process.
Methods: A single or repeated oral gavages with Porphyromonas gingivalis (Pg) 53977 were administrated into mice. Systemic and local immune responses were analyzed by flow cytometry and ELISA, gene expression assessed by qRT-PCR, as well as alveolar bone loss (ABL) using µCT.
Results: Considerable ABL was observed only following repeated administration of Pg, indicating the presence of destructive immunity. Systemically,higher Pg-specific IgG1 and IgG2a titers and IFN-γ levels were found in mice repeatedly exposed to Pg. Moreover a robust th1-type response was developed in repeatedly-infected mice, which also have an unexpected capacity to secrete high levels of IFN-γ spontaneously. Further examination revealed that due to the repetitive exposure to Pg, the type of DC migrating to the gingival-draining lymph nodes (LN), as well as their maturation state, changed dramatically, resulting in an hyper-activation of CD4⁺T cells into Th1 effector cells. As a result of this activation elevated numbers of RANKL-expressing CD4⁺T cells accumulated in the gingiva which mediate ABL.
Conclusions: In the course of repeated exposures to periopathogen, the type of DC in the gingiva is altered after each inoculation due to infiltration of new DC precursors and departure of pathogen-experienced DC to the LNs. This results in a robust and chronic activation of RANKL-expressing CD4⁺T cells that facilitate ABL.