Gekara Nelson O, Jacobs Thomas, Chakraborty Trinad, Weiss Siegfried
Molecular Immunology, German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany.
Cell Microbiol. 2005 Sep;7(9):1345-56. doi: 10.1111/j.1462-5822.2005.00561.x.
The pore-forming toxin listeriolysin O (LLO) is the main virulence factor of Listeria monocytogenes. LLO is known to act as a pseudo cytokine/chemokine, which induces a broad spectrum of host responses that ultimately influences the outcome of listeriosis. In the present study we demonstrate that LLO is a potent aggregator of lipid rafts. LLO was found to aggregate the raft associated molecules GM1, the GPI-anchored proteins CD14 and CD16 as well as the tyrosine kinase Lyn. Abrogation of the cytolytic activity of LLO by cholesterol pretreatment was found not to interfere with LLO's ability to aggregate rafts or trigger tyrosine phosphorylation in cells. However, a monoclonal antibody that blocks the oligomerization of LLO was found to inhibit rafts' aggregation as well as the induction of tyrosine phosphorylation. This implies that rafts aggregation by LLO which is independent of cytolytic activity, is due to the oligomerization of its membrane bound toxin monomers. Thus, LLO most likely induces signalling through the coaggregation of rafts' associated receptors, kinases and adaptors.
成孔毒素李斯特菌溶血素O（LLO）是单核细胞增生李斯特菌的主要毒力因子。已知LLO可作为一种假细胞因子/趋化因子，诱导广泛的宿主反应，最终影响李斯特菌病的结局。在本研究中，我们证明LLO是脂筏的有效聚集剂。发现LLO可聚集与脂筏相关的分子GM1、糖基磷脂酰肌醇（GPI）锚定蛋白CD14和CD16以及酪氨酸激酶Lyn。通过胆固醇预处理消除LLO的溶细胞活性，发现这并不影响LLO聚集脂筏或触发细胞内酪氨酸磷酸化的能力。然而，发现一种阻断LLO寡聚化的单克隆抗体可抑制脂筏聚集以及酪氨酸磷酸化的诱导。这意味着LLO诱导的脂筏聚集独立于溶细胞活性，是由于其膜结合毒素单体的寡聚化。因此，LLO很可能通过脂筏相关受体、激酶和衔接蛋白的共聚集来诱导信号传导。
