Riedel D D, Kaufmann S H
Department of Immunobiology, University Leipzig, Talstr. 33,04103, Leipzig, Germany.
Microbes Infect. 2000 Apr;2(5):463-71. doi: 10.1016/s1286-4579(00)00319-1.
Various bacterial cell wall components have been shown to induce hyporesponsiveness in macrophages (MAC). Here, mycobacterial glycolipids were employed to determine whether they induce a state of 'tolerance/hyporesponsiveness' in MAC in vitro in order to assess whether mycobacterial components negatively affect the immune response to Mycobacterium tuberculosis. Arabinosylated lipoarabinomannan (ARA-LAM) stimulated hyporesponsiveness by reducing TNF-alpha, GM-CSF, G-CSF, IL-10, and IL-6 release similarly to LPS, but caused no changes in IL-8 secretion. Mannose-capped LAM (MAN-LAM) acted in a different way in that TNF-alpha, GM-CSF, and IL-10 were upregulated after restimulation of MAC. Blocking experiments by mannan suggest mannose-receptor involvement in MAN-LAM activation only. Cross-stimulation experiments demonstrated a hierarchy of signaling, with LPS being the most potent stimulator and mediating abrogation of ARA-LAM-stimulated tolerance but not vice versa. MAN-LAM was the least potent stimulator of either MAC activation and induction of hyporesponsiveness. Similarly to LPS, ARA-LAM upregulated CD14 surface expression after restimulation. Recurrent MAN-LAM treatment either downmodulated or did not induce any change in CD14 expression. The role of MAN-LAM regulated cytokine secretion as well as implications regarding M. tuberculosis infection will be discussed.
多种细菌细胞壁成分已被证明可诱导巨噬细胞（MAC）反应低下。在此，利用分枝杆菌糖脂来确定它们是否在体外诱导MAC处于“耐受/反应低下”状态，以便评估分枝杆菌成分是否会对结核分枝杆菌的免疫反应产生负面影响。阿拉伯糖基化脂阿拉伯甘露聚糖（ARA-LAM）通过降低TNF-α、GM-CSF、G-CSF、IL-10和IL-6的释放来刺激反应低下，其作用方式与LPS类似，但对IL-8分泌无影响。甘露糖封端的LAM（MAN-LAM）的作用方式不同，在再次刺激MAC后，TNF-α、GM-CSF和IL-10会上调。甘露聚糖阻断实验表明甘露糖受体仅参与MAN-LAM的激活。交叉刺激实验证明了信号传导的层级关系，LPS是最有效的刺激物，可介导ARA-LAM刺激的耐受性的消除，但反之则不然。MAN-LAM是MAC激活和诱导反应低下的最无效刺激物。与LPS类似，再次刺激后ARA-LAM上调CD14表面表达。反复给予MAN-LAM处理可下调CD14表达或使其无变化。将讨论MAN-LAM调节细胞因子分泌的作用以及对结核分枝杆菌感染的影响。
