Redecke Vanessa, Häcker Hans, Datta Sandip K, Fermin Agnes, Pitha Paula M, Broide David H, Raz Eyal
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
J Immunol. 2004 Mar 1;172(5):2739-43. doi: 10.4049/jimmunol.172.5.2739.
Recognition of microbial components by APCs and their activation through Toll-like receptors (TLR) leads to the induction of adaptive immune responses. In this study, we show that activation of TLR2 by its synthetic ligand Pam3Cys, in contrast to activation of TLR9 by immunostimulatory DNA (ISS-ODN), induces a prominent Th2-biased immune response. Activation of APCs by Pam3Cys resulted in the induction of Th2-associated effector molecules like IL-13, and IL-1beta, GM-CSF and up-regulation of B7RP-1, but low levels of Th1-associated cytokines (IL-12, IFNalpha, IL-18, IL-27). Accordingly, TLR2 ligands aggravated experimental asthma. These data indicate that the type of TLR stimulation during the initial phase of immune activation determines the polarization of the adaptive immune response and may play a role in the initiation of Th2-mediated immune disorders, such as asthma.
抗原呈递细胞（APC）对微生物成分的识别以及通过Toll样受体（TLR）对其进行激活会导致适应性免疫反应的诱导。在本研究中，我们发现其合成配体Pam3Cys对TLR2的激活，与免疫刺激DNA（ISS-ODN）对TLR9的激活相反，会诱导显著的Th2偏向性免疫反应。Pam3Cys对APC的激活导致Th2相关效应分子如IL-13、IL-1β、GM-CSF的诱导以及B7RP-1的上调，但Th1相关细胞因子（IL-12、IFNα、IL-18、IL-27）水平较低。相应地，TLR2配体加重了实验性哮喘。这些数据表明，免疫激活初始阶段的TLR刺激类型决定了适应性免疫反应的极化，并且可能在Th2介导的免疫紊乱如哮喘的起始中发挥作用。
