Toll-Like Receptor Signaling in the Pathogenesis of Chronic Dacryocystitis: Implication of c-FOS Transcription Factor and its Downstream Effector Chemokine Genes CCL2, CCL4, CXCL3, CXCR4 with a Shift of the M1/M2 Macrophage Phenotype

Introduction TLRs are fundamental elements in the orchestration of the innate immune system. These receptors seem to be responsible for the inflammation and fibrosis in chronic dacryocystitis. The aim of the present study was to investigate the role of the toll-Like receptors (TLR2 and TLR4) signaling pathway and its downstream effector chemokine genes in the pathogenesis of chronic dacryocystitis. Methods This study was conducted on 20 patients diagnosed with chronic dacryocystitis and \nunderwent external dacryocystorhinostomy. Estimation of gene expression of TLR2, TLR4, CCL2, CCL4, CXCL3, CXCR4, and c-FOS genes in the lacrimal sac tissues was performed together with the assessment of the inflammatory markers TNF alpha, IL-1 beta, IFN-gamma, and IL-22. Histopathological examination of the lacrimal sac walls using hematoxylin and eosin (H&E) stain, in addition to \nimmunohistochemical staining of the CD68 and CD163 macrophage markers, was also performed. Results Our results showed that TLR2, TLR4, and c-FOS gene expressions were significantly increased in the chronic dacryocystitis group with a subsequent increase in their downstream effector chemokine genes CCL2, CCL4, and CXCL3. This up-regulation of genes was accompanied by macrophage shift of polarization toward the M1 pro-inflammatory phenotype (increased CD68 and decreased CD163 expression), leading to increased levels of the pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IFN-gamma) and decreased anti-inflammatory marker IL-22 with chronic dacryocystitis. Conclusion It is essential to fine-tune TLR activation through emerging therapeutic approaches. Targeting TLR signaling at the level of receptors or downstream adaptor molecules represents a new challenge for treating chronic dacryocystitis.

Automated summary

This study aimed to investigate the role of TLR2 and TLR4 signaling pathway and its downstream effector chemokine genes in the pathogenesis of chronic dacryocystitis. It was found that TLR2, TLR4, and c-FOS gene expressions were significantly increased in the chronic dacryocystitis group, accompanied by an increase in their downstream effector chemokine genes CCL2, CCL4, and CXCL3.