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Toll-like receptors (TLRs) participate in the innate immune response and trigger the immune responses of the body. Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown aetiology, characterized by an excessive autoimmune response in the body affecting the connective tissues. The disease is possibly triggered by both environmental aetiological factors and pathological organic processes such as exposure to sunlight, chronic infectious processes and genetic factors. Conversely, periodontal disease is an infectious disease caused by microorganisms in the oral cavity, resulting in a chronic inflammatory process which continuously stimulates the immune response, thus causing damage to the periodontal tissues. The expression of both TLR-2 and TLR-4 receptors are increased in both SLE and periodontal disease. Periodontitis might trigger excessive activation of immune response occurring in SLE by maintaining a high expression of TLRs, leading in turn to the acceleration of the onset and progression of autoimmune reactions. In addition, periodontal treatment is able to reduce the expression of these receptors and therefore the symptoms of SLE. Here we discuss the possible interaction between SLE and periodontitis, and suggest further studies evaluating common features in both factors that could explored, due to morbidity and mortality of SLE and the high incidence of periodontal infections around the world.