Polycarpou Anastasia, Holland Martin J, Karageorgiou Ioannis, Eddaoudi Ayad, Walker Stephen L, Willcocks Sam, Lockwood Diana N J
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine London, UK.
Molecular and Cellular Immunology Unit, Institute of Child Health, University College London London, UK.
Front Cell Infect Microbiol. 2016 Jul 8;6:72. doi: 10.3389/fcimb.2016.00072. eCollection 2016.
Toll-like receptor (TLR)-1 and TLR2 have been shown to be receptors for Mycobacterium leprae (M. leprae), yet it is unclear whether M. leprae can signal through alternative TLRs. Other mycobacterial species possess ligands for TLR4 and genetic association studies in human populations suggest that people with TLR4 polymorphisms may be protected against leprosy. Using human embryonic kidney (HEK)-293 cells co-transfected with TLR4, we demonstrate that M. leprae activates TLR4. We used human macrophages to show that M. leprae stimulation of cytokine production is diminished if pre-treated with TLR4 neutralizing antibody. TLR4 protein expression was up-regulated on macrophages derived from non-bacillus Calmette-Guerin (BCG) vaccinated healthy volunteers after incubation with M. leprae, whereas it was down-regulated in macrophages derived from BCG-vaccinated donors. Finally, pre-treatment of macrophages derived from BCG-naive donors with BCG reversed the effect of M. leprae on TLR4 expression. This may be a newly described phenomenon by which BCG vaccination stimulates "non-specific" protection to the human immune system.
Toll样受体（TLR）-1和TLR2已被证明是麻风分枝杆菌的受体，但尚不清楚麻风分枝杆菌是否能通过其他TLR发出信号。其他分枝杆菌物种拥有TLR4的配体，人群中的基因关联研究表明，具有TLR4多态性的人可能对麻风病具有抵抗力。通过使用与TLR4共转染的人胚肾（HEK）-293细胞，我们证明麻风分枝杆菌可激活TLR4。我们用人巨噬细胞表明，如果用TLR4中和抗体预处理，麻风分枝杆菌对细胞因子产生的刺激作用会减弱。与麻风分枝杆菌孵育后，未接种卡介苗（BCG）的健康志愿者来源的巨噬细胞上TLR4蛋白表达上调，而接种BCG的供体来源的巨噬细胞中TLR4蛋白表达下调。最后，用BCG预处理未接触过BCG的供体来源的巨噬细胞可逆转麻风分枝杆菌对TLR4表达的影响。这可能是一种新描述的现象，即BCG疫苗接种对人类免疫系统产生“非特异性”保护作用。
