Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to a great extent on the innate immune response against mycobacteria. Host defense peptides (HDP) are one of the first barriers to counteract infection. Cathelicidin (LL-37) is an HDP that has many immunomodulatory effects besides its weak antimicrobial activity. Despite advances in the study of the innate immune response in tuberculosis, the immunological role of LL-37 during M. tuberculosis infection has not been clarified. Monocyte-derived macrophages were infected with M. tuberculosis strain H37Rv and then treated with 1, 5, or 15 g/ml of exogenous LL-37 for 4, 8, and 24 h. Exogenous LL-37 decreased tumor necrosis factor alpha (TNF-␣) and interleukin-17 (IL-17) while inducing anti-inflammatory IL-10 and transforming growth factor  (TGF-) production. Interestingly, the decreased production of anti-inflammatory cytokines did not reduce antimycobacterial activity. These results are consistent with the concept that LL-37 can modulate the expression of cytokines during mycobacterial infection and this activity was independent of the P2X7 receptor. Thus, LL-37 modulates the response of macrophages during infection, controlling the expression of proinflammatory and anti-inflammatory cytokines.T uberculosis (TB), caused by Mycobacterium tuberculosis, is the single deadliest communicable disease. In 2013, an estimated 9.0 million people developed TB and 1.5 million died from the disease (1).The main cells involved in the control of tuberculosis are macrophages, and together with epithelial cells, they are the first antiinfective immunological barriers encountered, with a primary task to initiate pathogen clearance. In the progress of cellular immunity against M. tuberculosis, macrophages can also function as antigen-presenting cells, in which the antigens of M. tuberculosis are degraded into immunogenic polypeptides and presented on T lymphocytes by the major histocompatibility complex to trigger adaptive immunity. However, M. tuberculosis has developed a wide assortment of strategies to counteract the bactericidal activities of these cells, enabling it to successfully establish a niche for long-term survival within macrophages. This M. tuberculosis replication causes mild inflammation, which promotes cell-mediated immunity that often leads to M. tuberculosis retention through granuloma (tubercle) formation (2). When infection becomes reactivated at a low rate, the granuloma suffers caseous necrosis, and this results in lung cavitation and pulmonary disease, inducing a prominent inflammation (3). Several molecules of the immune system are involved throughout this process, including host defense peptides (HDP) such as cathelicidin and defensins (4-6).LL-37 is the unique member of cathelicidin family in humans; this multifunctional immunomodulatory HDP is produced mainly by phagocytic leukocytes and epithelial cells as well as being normally found at concentrations varying from 2 to 5 g/ml in several fl...
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