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Background: Nucleic acid sensing has emerged as one of the important components of the immune system triggering inflammation. The aim of this study is to determine the expression of bacterial DNA sensors, including Toll-like receptor 9 (TLR-9), DNA-dependent activator of interferon-regulatory factors (DAI), and absent in melanoma 2 (AIM2) in chronic periodontitis (CP versus healthy) (H) tissues., Methods: Thirty-five CP and 27 H gingival biopsies were included. Real-time quantitative polymerase chain reaction was performed to determine mRNA levels of AIM2, DAI, and TLRs (TLR-1 through TLR-9). The difference in gene expression for each sensor between CP and H tissues was calculated using analysis of covariance. The Spearman test was used to determine correlations among innate receptors. The expression of TLR-9, AIM2, and DAI in gingival tissues was further confirmed using immunohistochemistry., Results: The present results reveal statistically significant upregulation of TLR-9 (P <0.006), DAI (P <0.001), and TLR-8 (P <0.01) in CP tissues compared to H sites. Although mRNA expression was not changed significantly between groups for other receptors, the present results reveal significant correlations between receptors (P <0.05), suggesting that cooperation between multiple components of the host immune system may influence the overall response. Immunohistochemistry further confirmed expression of TLR-9, AIM2, and DAI in gingival tissues., Conclusions: This study highlights a possible role for nucleic acid receptors in periodontal inflammation. Future investigations will determine whether cytoplasmic receptors and their ligands can be targeted to improve clinical outcomes in periodontitis.