刚地弓形虫暴露磷脂酰丝氨酸，诱导转化生长因子-β1自分泌效应，从而精心策划巨噬细胞逃避。
Toxoplasma gondii exposes phosphatidylserine inducing a TGF-beta1 autocrine effect orchestrating macrophage evasion.
作者信息
Seabra Sergio H, de Souza Wanderley, Damatta Renato A
机构信息
Laboratório de Biologia Celular e Tecidual, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense, 28013-600 Campos dos Goytacazes, RJ, Brazil.
出版信息
Biochem Biophys Res Commun. 2004 Nov 12;324(2):744-52. doi: 10.1016/j.bbrc.2004.09.114.
Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii. Activated macrophages control T. gondii growth by nitric oxide (NO) production. However, T. gondii active invasion inhibits NO production, allowing parasite persistence. Here we show that the mechanism used by T. gondii to inhibit NO production persisting in activated macrophages depends on phosphatidylserine (PS) exposure. Masking PS with annexin-V on parasites or activated macrophages abolished NO production inhibition and parasite persistence. NO production inhibition depended on a transforming growth factor-beta1 (TGF-beta1) autocrine effect confirmed by the expression of Smad 2 and 3 in infected macrophages. TGF-beta1 led to inducible nitric oxide synthase (iNOS) degradation, actin filament (F-actin) depolymerization, and lack of nuclear factor-kappaB (NF-kappaB) in the nucleus. All these features were reverted by TGF-beta1 neutralizing antibody treatment. Thus, T. gondii mimics the evasion mechanism used by Leishmania amazonensis and also the anti-inflammatory response evoked by apoptotic cells.
弓形虫病是一种由刚地弓形虫引起的全球性疾病。活化的巨噬细胞通过产生一氧化氮（NO）来控制刚地弓形虫的生长。然而，刚地弓形虫的主动入侵会抑制NO的产生，从而使寄生虫得以持续存在。在此我们表明，刚地弓形虫在活化巨噬细胞中持续抑制NO产生所采用的机制取决于磷脂酰丝氨酸（PS）的暴露。用膜联蛋白-V掩盖寄生虫或活化巨噬细胞上的PS可消除NO产生的抑制作用和寄生虫的持续存在。NO产生的抑制作用取决于转化生长因子-β1（TGF-β1）的自分泌效应，这在感染巨噬细胞中Smad 2和3的表达得到证实。TGF-β1导致诱导型一氧化氮合酶（iNOS）降解、肌动蛋白丝（F-肌动蛋白）解聚以及细胞核中缺乏核因子-κB（NF-κB）。所有这些特征都可通过TGF-β1中和抗体治疗得以恢复。因此，刚地弓形虫模仿了亚马逊利什曼原虫所采用的确逃避机制以及凋亡细胞所引发的抗炎反应。
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