RESUMO
The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.
Assuntos
Peptídeos Catiônicos Antimicrobianos/biossíntese , Células Epiteliais/imunologia , Macrófagos Alveolares/imunologia , Monócitos/imunologia , Mycobacterium tuberculosis/imunologia , Neutrófilos/imunologia , Lavagem Broncoalveolar , Linhagem Celular , Células Cultivadas , Citoplasma/química , Células Epiteliais/química , Células Epiteliais/microbiologia , Perfilação da Expressão Gênica , Granuloma/genética , Humanos , Imuno-Histoquímica , Macrófagos Alveolares/química , Macrófagos Alveolares/microbiologia , Microscopia Imunoeletrônica , Monócitos/química , Monócitos/microbiologia , Neutrófilos/química , Neutrófilos/microbiologia , Receptores Toll-Like/imunologia , CatelicidinasRESUMO
The kinetics of gene expression and the cellular source of murine beta -defensin-3 (mBD3) and murine beta -defensin-4 (mBD4) were determined in mouse models of progressive pulmonary tuberculosis and latent infection induced by high or low infecting doses, respectively. During progressive disease, there was an initial rapid expression of both defensins by respiratory epithelial cells that correlated with temporary control of bacillary proliferation, but expression decreased during the later progressive phase of the disease. In latent infection, both defensins were expressed continuously, but they were suppressed after reactivation of the disease. Thus, mycobacterial infection induces the expression of mBD3 and mBD4, and both might participate in the control of mycobacterial growth.