Godaly Gabriela, Young Douglas B
Department of Infectious Diseases and Microbiology, Division of Investigative Science, Faculty of Medicine, Imperial College London, UK.
Cell Microbiol. 2005 Apr;7(4):591-601. doi: 10.1111/j.1462-5822.2004.00489.x.
To investigate the potential role of neutrophils in initiation of immune responses to mycobacteria, we have characterized the response of human neutrophils to infection with Mycobacterium bovis bacille Calmette Guerin, the BCG vaccine. BCG induced transcription and secretion of the chemokine CXCL8, by signalling through Toll-like receptors TLR2 and TLR4, in conjunction with the adaptor protein myeloid differentiation factor 88 (MyD88). Blocking of responses with antibodies revealed a difference in the kinetics of signalling through the different TLRs. Anti-TLR2 antibody blocked the early phase of CXCL8 and MyD88 induction. Anti-TLR4 antibody blocked the late phase of induction occurring 2 h after infection. The existence of a TLR/MyD88 pathway for recognition and response to mycobacterial ligands provides neutrophils with the ability to drive the recruitment and activation of inflammatory cells during the early phase of mycobacterial infection and immunization.
为了研究中性粒细胞在启动针对分枝杆菌的免疫反应中的潜在作用，我们对人类中性粒细胞对卡介苗（BCG疫苗）感染的反应进行了表征。卡介苗通过Toll样受体TLR2和TLR4信号传导，并与衔接蛋白髓样分化因子88（MyD88）结合，诱导趋化因子CXCL8的转录和分泌。用抗体阻断反应揭示了通过不同TLR信号传导动力学的差异。抗TLR2抗体阻断了CXCL8和MyD88诱导的早期阶段。抗TLR4抗体阻断了感染后2小时出现的诱导后期阶段。存在用于识别和响应分枝杆菌配体的TLR/MyD88途径，使中性粒细胞能够在分枝杆菌感染和免疫的早期阶段驱动炎症细胞的募集和激活。
