TLR4 expression and its immunopathogenic role in inflammatory radicular cysts: a clinicopathological study

Inflammatory radicular cysts are among the most frequently diagnosed odontogenic cysts and arise as a consequence of chronic periapical inflammation of endodontic origin. Their development and persistence are associated with continuous microbial stimulation and activation of local immune responses. Toll-like receptor 4 (TLR4) is a member of the pattern recognition receptor (PRR) family. In periapical pathology, TLR4 is essential for detecting microbial antigens derived from the infected root canal system. The purpose of this study was to evaluate the immunohistochemical (IHC) expression of TLR4 in inflammatory radicular cysts and to assess its involvement in the local inflammatory response. Biopsy specimens from 39 patients diagnosed with radicular cysts were processed for routine histological examination and IHC analysis using anti-TLR4 antibodies. Histological evaluation revealed a chronic lymphoplasmacytic inflammatory infiltrate with a high density of macrophage-like cells and large mononuclear cells in all samples. IHC findings demonstrated strong cytoplasmic TLR4 expression in macrophage-like cells and large mononuclear cells, key innate immune cells, along with a discrete membranous distribution, supporting active recognition of pathogen-associated molecular patterns. Moderate TLR4 expression was also observed in neutrophils, suggesting focal areas of acute inflammatory activity superimposed on a chronic inflammatory background. These results indicate that TLR4 plays a significant role in the immunopathogenesis of inflammatory radicular cysts by mediating innate immune activation and sustaining local inflammation. A better understanding of TLR4 signaling involvement may contribute to improved insights into lesion behavior and support future targeted therapeutic approaches aimed at modulating persistent inflammatory processes in periapical pathology.