HIV-1感染導(dǎo)致機(jī)體免疫系統(tǒng)被破壞不能有效抵御其它病原微生物的入侵,。病原微生物的侵染已被認(rèn)為是機(jī)體免疫激活的重要標(biāo)志,而機(jī)體的免疫激活可能更進(jìn)一步增強(qiáng)HIV-1的復(fù)制和傳播,。但機(jī)會性病原體如何加速免疫系統(tǒng)的破壞尚不明確,。
樹突狀細(xì)胞(DC)是機(jī)體重要的抗原遞呈細(xì)胞,在免疫防御中起到重要作用,。但在HIV-1感染中,,DC卻起到了雙刃劍作用。DC能被病毒調(diào)控以抑制機(jī)體的抗病毒免疫反應(yīng),,也能夠被HIV-1利用增加病毒的傳播,。因此,研究DC-HIV-1的相互作用對于病毒致病機(jī)理的闡述非常重要,。
中科院上海巴斯德研究所病毒免疫學(xué)研究組博士生秦琰在導(dǎo)師王建華研究員的指導(dǎo)下,,從艾滋病人皮損組織中分離出隱球菌。隱球菌是一種艾滋病常見的機(jī)會性真菌病原體,。研究發(fā)現(xiàn),,隱球菌能夠促進(jìn)DC的成熟從而增加HIV-1至T細(xì)胞的傳播,并能加速靜息T細(xì)胞的活化而增加對HIV-1的易感性,。研究結(jié)果在一定程度上解釋了機(jī)會性病原體如何加速病毒復(fù)制和增加病毒載量的機(jī)制,,揭示了病毒的致病機(jī)理。
研究結(jié)果于2012年6月發(fā)表于學(xué)術(shù)期刊Biochem Biophys Res Commun,。該項研究與昆明醫(yī)學(xué)院第一附屬醫(yī)院合作,,并得到了來自中科院、國家基金委及上海市等項目資助,。(生物谷Bioon.com)
doi:10.1016/j.bbrc.2012.06.020
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Stimulation of Cryptococcus neoformans isolated from skin lesion of AIDS patient matures dendritic cells and promotes HIV-1 trans-infection
Yan Qinb, c, 1, Yu-Ye Lia, 1, Ai-ping Jiangb, c, Jin-Feng Jiangb, Jian-Hua Wangb, ,
Dendritic cells (DCs) play a pivotal role in host defense against invaded pathogens including fungi, while DCs are targeted by fungi for deleterious regulation of the host immune response. A few studies have reported fungal modulation of DC function in these immunocompromised AIDS patients. Cryptococcus neoformans (C. neoformans) is referred as one of the opportunistic fungi of AIDS. Here, we isolated native C. neoformans from an AIDS patient and investigated its effects on DC activation and function. Stimulation of C. neoformans matured DCs, and enhanced DC-mediated HIV-1 trans-infection; moreover, C. neoformans-stimulated DCs promoted the activation of resting T cells and provided more susceptible targets for HIV-1 infection. Microbial translocation has been proposed as the cause of systemic immune activation in chronic HIV-1 infection. Understanding the potential effects of pathogens on HIV-1-DC interactions could help elucidate viral pathogenesis and provide a new insight for against the spread of HIV.