弓形蟲依靠其獨特肌動蛋白的滑行運動形式,幾乎能夠感染所有的有核細胞,,滑動是跨越生物屏障與入侵宿主細胞以及從宿主細胞出來的主要運動方式,。
Plattner等人的最新研究表明,,弓形蟲中的Profilin蛋白是肌動蛋白動力的調(diào)制器,,它是調(diào)節(jié)寄生蟲動力的關(guān)鍵蛋白,,同時又是Toll樣受體激動劑,,刺激白介素-12產(chǎn)生和調(diào)節(jié)宿主先天免疫反應(yīng),。封面圖片顯示了蟲空泡在成纖維細胞含有復(fù)制弓形蟲速殖子。這種寄生蟲主要表面抗原SAG1已經(jīng)被抗體染色,,表現(xiàn)為紅色,。
頂配位寄生蟲顯示出肌動蛋白依賴型的滑行運動,這種滑行運動是跨越生物屏障與入侵宿主細胞的關(guān)鍵,。其中肌動蛋白聚合的主要貢獻者是Profilins蛋白,,而弓形蟲擁有可以被宿主先天免疫系統(tǒng)中Toll樣受體11(TLR11)識別的Profilin蛋白。Plattner等人通過一系列巧妙的方法干擾弓形蟲Profilin蛋白的相應(yīng)基因,,讓Profilin蛋白無法在細胞內(nèi)生長,,而必須通過滑行運動入侵宿主細胞,然后從宿主細胞出來,,對實驗小鼠產(chǎn)生毒性,。
研究發(fā)現(xiàn),缺乏Profilin蛋白的寄生蟲不能在胞外誘導依賴型TLR11的產(chǎn)生,,也無法刺激胞內(nèi)防御性的宿主細胞因子白細胞介素-12產(chǎn)生TLR11,。因此,Profilin蛋白可以使宿主細胞從兩方面感染弓形蟲,,也就是說,,Profilin就像細菌的鞭毛一樣,在為寄生蟲的滑行運動提供動力的同時,,還是宿主細胞先天免疫系統(tǒng)識別的微生物配體,。
相關(guān)研究論文發(fā)表在2月14日的《細胞—宿主與微生物》(Cell Host & Microbe)上。(科學網(wǎng) 武彥文/編譯)
生物谷推薦原始出處:
(Cell Host & Microbe),,Vol 3, 77-87, 14 February 2008,,F(xiàn)abienne Plattner, Dominique Soldati-Favre
Toxoplasma Profilin Is Essential for Host Cell Invasion and TLR11-Dependent Induction of an Interleukin-12 Response
Fabienne Plattner, Felix Yarovinsky, Stephane Romero, Dominique Didry, Marie-France Carlier, Alan Sher, and Dominique Soldati-Favre,
Summary
Apicomplexan parasites exhibit actin-dependent gliding motility that is essential for migration across biological barriers and host cell invasion. Profilins are key contributors to actin polymerization, and the parasite Toxoplasma gondii possesses a profilin-like protein that is recognized by Toll-like receptor TLR11 in the host innate immune system. Here, we show by conditional disruption of the corresponding gene that T.gondii profilin, while not required for intracellular growth, is indispensable for gliding motility, host cell invasion, active egress from host cells, and virulence in mice. Furthermore, parasites lacking profilin are unable to induce TLR11-dependent production in vitro and in vivo of the defensive host cytokine interleukin-12. Thus, profilin is an essential element of two aspects of T. gondii infection. Like bacterial flagellin, profilin plays a role in motility while serving as a microbial ligand recognized by the host innate immune system.