OBJECTIVESSystemic lupus erythematosus (SLE) is associated with the activation of both innate and adaptive immune system. Infection is a significant environmental factor that is responsible for the development of SLE. Toll-like receptors (TLRs) are responsible for recognizing pathogens, and the expression of TLRs has been found to differ in SLE patients. Additionally, various infections have been reported to influence TLR expression. This study aimed to explore the relationship between TLRs and the onset, severity, and symptoms of SLE in the eastern Indian population.METHODSThe study included 70 SLE patients and a control group matched for age and sex. RT-PCR was used to evaluate mRNA expression of TLRs 2, 4, 7, and 9. Statistical analyses were performed using GraphPad Prism software v.10.2.3.RESULTSPatients with SLE expressed significantly higher levels of TLR2 (p < 0.0001) and TLR9 (p = 0.012) than healthy controls. In lupus nephritis, TLR9 expression was higher than in SLE patients without kidney involvement (p = 0.037). Furthermore, a significant relationship was found between TLR9 expression and systemic lupus erythematosus disease activity index (SLEDAI) scores (p < 0.0001, Spearman's r = 0.47), implying the potential role of TLRs in SLE development. However, mRNA expression of TLR4 and TLR7 was not associated with SLE, clinical indices, or disease severity.CONCLUSIONSTLR9 is associated with SLE pathogenesis and clinical severity, making it a promising molecule for targeted therapy in SLE management.