Gomes M Salomé, Sousa Fernandes Sofia, Cordeiro João V, Silva Gomes Sandro, Vieira André, Appelberg Rui
Laboratory of Microbiology and Immunology of Infection, IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal.
Eur J Immunol. 2008 Aug;38(8):2180-9. doi: 10.1002/eji.200737954.
Toll-like receptor (TLR) 2 plays an important role in the immune response to mycobacterial infections, being required for optimal immunity against certain virulent Mycobacterium avium strains. Here we analyzed the role of TLR2 in the intra-macrophagic growth of M. avium, using macrophages from TLR2-deficient mice. We found that the engagement of TLR2/TLR6 and/or TLR2/TLR1 receptors induced bacteriostasis of M. avium inside bone marrow-derived macrophages in a MyD88-dependent way. Additionally, lipoproteins from the cell envelope of M. avium with a molecular mass of 20-25 kDa triggered this TLR2 pathway, leading to a decrease in the growth of the mycobacteria. Although TLR2 engagement induced the production of TNF, this cytokine as well as nitric oxide and superoxide molecules were not necessary for TLR2-mediated bacteriostasis. Finally, TLR ligation did not induce the expression of the 47-kDa guanosine triphosphatase (LRG-47) but it promoted an increased maturation of the phagosome with regards to acquisition of LAMP1. Our data show that triggering TLR2 inhibited M. avium growth by an as-yet-unknown mechanism that may involve increased phagosome maturation.
Toll样受体（TLR）2在针对分枝杆菌感染的免疫反应中发挥重要作用，是抵抗某些致病性鸟分枝杆菌菌株的最佳免疫所必需的。在此，我们使用来自TLR2缺陷小鼠的巨噬细胞，分析了TLR2在鸟分枝杆菌巨噬细胞内生长中的作用。我们发现，TLR2/TLR6和/或TLR2/TLR1受体的激活以MyD88依赖的方式诱导骨髓来源巨噬细胞内鸟分枝杆菌的抑菌作用。此外，来自鸟分枝杆菌细胞包膜的分子量为20 - 25 kDa的脂蛋白触发了该TLR2途径，导致分枝杆菌生长减少。尽管TLR2的激活诱导了TNF的产生，但该细胞因子以及一氧化氮和超氧化物分子对于TLR2介导的抑菌作用并非必需。最后，TLR连接未诱导47 kDa鸟苷三磷酸酶（LRG - 47）的表达，但就LAMP1的获得而言，它促进了吞噬体成熟的增加。我们的数据表明，触发TLR2通过一种未知机制抑制鸟分枝杆菌生长，该机制可能涉及吞噬体成熟增加。
