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Objective: This study was designed to examine the potential ability of Candida albicans DNA to influence joint inflammation in a mouse model of zymosan-induced arthritis (ZIA) relating to Toll-like receptor-9 (TLR9) expression and cytokine production in different compartments., Methods: To induce ZIA, mice were injected in the ankle joint with 180 μg zymosan. TLR9 expression in synovial extracts, peritoneal macrophages, splenocytes and popliteal lymph node cells was analyzed by flow cytometry. The levels of interferon (IFN)-γ, interleukin (IL)-6 and IL-10 in synovial fluid and sera were measured by ELISA. The expression of TLR9 in the joints was determined by immunohistochemistry., Results: A single intraperitoneal injection of C. albicans DNA did not elevate TLR9 expression and cytokine levels in the joints. It increased TLR9 expression by peritoneal macrophages isolated from healthy and arthritic mice and elevated the IFN-γ level in circulation. In-vitro stimulation with DNA enhanced IL-6, IFN-γ and IL-10 production by different cells isolated from mice with ZIA., Conclusion: These results suggest that small quantities of C. albicans DNA can provoke a pro-inflammatory systemic response rather than locally in the joint.