Rocha-Ramírez Luz María, Estrada-García Iris, López-Marín Luz María, Segura-Salinas Erika, Méndez-Aragón Patricia, Van Soolingen Dick, Torres-González Rubén, Chacón-Salinas Rommel, Estrada-Parra Sergio, Maldonado-Bernal Carmen, López-Macías Constantino, Isibasi Armando
Departamento de Infectología, Hospital Infantil de México, Secretaría de Salud, México D.F., Mexico.
Tuberculosis (Edinb). 2008 May;88(3):212-20. doi: 10.1016/j.tube.2007.10.003. Epub 2008 Jan 28.
The interaction of macrophages with Mycobacterium tuberculosis through Toll-like receptors is critical in defining the cytokine profile that may or may not control disease progression. Cell-wall lipids are the main pathogen-associated molecular ligands of mycobacteria, in this paper, we analysed how lipid fractions of three different strains of the M. tuberculosis complex (genotypes Canetti, Beijing and H37Rv) affected the innate immunity by regulating TNF-alpha and IL-10 secretion, TLR2, TLR4, and MHC class II expression of human monocyte-derived macrophages. Of note, lipid fractions from the Beijing genotype (hypervirulent phenotype) preferentially induced macrophages to secrete high amounts of TNF-alpha and IL-10, but downregulated TLR2, TLR4 and MHC class II expression. In contrast, lipids from M. tuberculosis Canetti induced lower amounts of TNF-alpha and IL-10, upregulated TLR2 and TLR4 without modifying MHC class II expression. These results indicate that the virulent mycobacterial genotype Beijing expresses lipids that negatively modified cytokine, TLR and MHC class II expression. These findings may help to unravel the complex mechanisms used by virulent mycobacteria to evade and subvert the immune response.
巨噬细胞通过Toll样受体与结核分枝杆菌的相互作用对于确定可能控制或无法控制疾病进展的细胞因子谱至关重要。细胞壁脂质是分枝杆菌主要的病原体相关分子配体，在本文中，我们分析了结核分枝杆菌复合群三种不同菌株（Canetti基因型、北京基因型和H37Rv）的脂质组分如何通过调节人单核细胞衍生巨噬细胞的TNF-α和IL-10分泌、TLR2、TLR4和MHC II类分子表达来影响固有免疫。值得注意的是，北京基因型（高毒力表型）的脂质组分优先诱导巨噬细胞分泌大量的TNF-α和IL-10，但下调TLR2、TLR4和MHC II类分子表达。相反，Canetti株结核分枝杆菌的脂质诱导产生的TNF-α和IL-10量较低，上调TLR2和TLR4，而不改变MHC II类分子表达。这些结果表明，高毒力的北京基因型分枝杆菌表达的脂质对细胞因子、TLR和MHC II类分子表达产生负面调节作用。这些发现可能有助于揭示高毒力分枝杆菌用于逃避和破坏免疫反应的复杂机制。
