2012年12月7日 訊 /生物谷BIOON/ --12月6日,，刊登在國(guó)際雜志PLoS Pathogens上的一篇研究報(bào)告首次揭示了，寄生蟲(chóng)-鼠弓形蟲(chóng)如何進(jìn)入到人類大腦中來(lái)影響宿主的行為表達(dá),，這項(xiàng)研究由瑞典卡羅林斯卡醫(yī)學(xué)院和烏普薩拉大學(xué)的研究者開(kāi)展,。
鼠弓形蟲(chóng)可以引發(fā)弓形體病，這種寄生蟲(chóng)比較常見(jiàn),，其可以感染全球30%至50%的人群,，同樣也可以感染動(dòng)物，如家貓,。人類通常由于食用感染且未熟的肉類以及處理家貓的糞便而感染鼠弓形蟲(chóng),，數(shù)項(xiàng)研究都表明，在鼠弓形蟲(chóng)休眠階段,，其感染人類的風(fēng)險(xiǎn)會(huì)大大增加,，而且使得感染者患精神分裂癥的發(fā)病率加大。
這項(xiàng)最新研究首次揭示了這種寄生蟲(chóng)如何進(jìn)入到人類的大腦中,，以及增加神經(jīng)遞質(zhì)GABA的釋放量,，GABA是一種gaba氨基丁酸的神經(jīng)遞質(zhì)，其可以抑制個(gè)體的焦慮和害怕的知覺(jué),。實(shí)驗(yàn)室研究中,，研究者用鼠弓形蟲(chóng)感染人類樹(shù)突細(xì)胞，樹(shù)突細(xì)胞是人類免疫防御的重要組分,，當(dāng)樹(shù)突細(xì)胞感染鼠弓形蟲(chóng)后,，就開(kāi)始釋放GABA到細(xì)胞中。在另一項(xiàng)小鼠實(shí)驗(yàn)中,，當(dāng)研究者將鼠弓形蟲(chóng)引入到小鼠大腦中后,，他們觀察了機(jī)體中受感染的樹(shù)突細(xì)胞的運(yùn)動(dòng)方式。
研究者Antonio Barragan說(shuō),，弓形體屬在感染細(xì)胞中分泌神經(jīng)遞質(zhì)GABA令人非常意外,，目前我們應(yīng)該研究在鼠弓形體、GABA系統(tǒng)以及公眾健康威脅之間的關(guān)系,。（生物谷Bioon.com）
doi:10.1371/journal.ppat.1003051
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GABAergic Signaling Is Linked to a Hypermigratory Phenotype in Dendritic Cells Infected by Toxoplasma gondii
Jonas M. Fuks1,2#, Romanico B. G. Arrighi1,2#, Jessica M. Weidner1,2#, Suresh Kumar Mendu3, Zhe Jin3, Robert P. A. Wallin1,4, Bence Rethi4, Bryndis Birnir3, Antonio Barragan1,2*
During acute infection in human and animal hosts, the obligate intracellular protozoan Toxoplasma gondii infects a variety of cell types, including leukocytes. Poised to respond to invading pathogens, dendritic cells (DC) may also be exploited by T. gondii for spread in the infected host. Here, we report that human and mouse myeloid DC possess functional γ-aminobutyric acid (GABA) receptors and the machinery for GABA biosynthesis and secretion. Shortly after T. gondii infection (genotypes I, II and III), DC responded with enhanced GABA secretion in vitro. We demonstrate that GABA activates GABAA receptor-mediated currents in T. gondii-infected DC, which exhibit a hypermigratory phenotype. Inhibition of GABA synthesis, transportation or GABAA receptor blockade in T. gondii-infected DC resulted in impaired transmigration capacity, motility and chemotactic response to CCL19 in vitro. Moreover, exogenous GABA or supernatant from infected DC restored the migration of infected DC in vitro. In a mouse model of toxoplasmosis, adoptive transfer of infected DC pre-treated with GABAergic inhibitors reduced parasite dissemination and parasite loads in target organs, e.g. the central nervous system. Altogether, we provide evidence that GABAergic signaling modulates the migratory properties of DC and that T. gondii likely makes use of this pathway for dissemination. The findings unveil that GABA, the principal inhibitory neurotransmitter in the brain, has activation functions in the immune system that may be hijacked by intracellular pathogens.
