Inflammatory Response To Porphyromonas Gingivalis Partially Requires Interferon Regulatory Factor (Irf) 3

Innate immune activation with expression of pro-inflammatory molecules such as TNF-alpha is a hallmark of the chronic inflammation associated with periodontal disease (PD). Porphyromonas gingivalis, a bacterium associated with PD, engages TLRs and activates MyD88-dependent and TIR-domain-containing adapter-inducing IFN-beta (TRIF)-dependent signaling pathways. IFN regulatory factor (IRF) 3 is activated in a TRIF-dependent manner and participates in production of cytokines such as TNF-alpha; however, little is known regarding IRF3 and the host response to PD pathogens. We speculated that IRF3 participates in the host inflammatory response to P. gingivalis. Our results show that bone marrow macrophages (Mo) from WT mice respond to P. gingivalis with activation and nuclear translocation of IRF3. Compared with WT, Mo from IRF3(-/-), TRIF-/-, and TLR4(-/-) mice responded with reduced levels of TNF-alpha on P. gingivalis challenge. In addition, full expression of IL-6 and RANTES by Mo to P. gingivalis was dependent on IRF3. Lastly, employing Mo from IRF3(-/-) and IRF7(-/-) mice we observed a significant role for IRF3 and a modest role for IRF7 in the P. gingivalis-elicited TNF-alpha response. These studies identify a role for IRF3 in the inflammatory response by Mo to the periodontal pathogen P. gingivalis.