近日，國(guó)際著名雜志PLoS ONE發(fā)表了中科院上海巴斯德所研究人員的研究成果“Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection by Activating Primary CD4+ T Cells,。”研究人員發(fā)現(xiàn),，P. marneffei刺激的DCs增加其表面黏附分子ICAM-1的表達(dá),，從而有效地增強(qiáng)與CD4+ T細(xì)胞的接觸，增強(qiáng)HIV-1從DCs至T細(xì)胞的傳播；
深部真菌馬爾尼菲青霉菌（P. marneffei)的感染，已成為繼肺結(jié)核桿菌和隱球菌外第三個(gè)最常見AIDS相關(guān)聯(lián)的機(jī)會(huì)性病原體感染性疾病,。機(jī)會(huì)性病原體如何加速免疫系統(tǒng)的過(guò)度激活從而促進(jìn)AIDS疾病進(jìn)程，目前尚未研究清楚,。
中科院上海巴斯德所博士研究生秦琰等在王建華研究員的指導(dǎo)下,，與相關(guān)單位合作，從P. marneffei與HIV-1共感染的病人皮膚損傷組織中分離出這一具有溫度雙相的真菌,，以其為代表分析了機(jī)會(huì)性病原體對(duì)樹突狀細(xì)胞（Dendritic Cell, DC)與HIV-1相互作用的影響,。他們發(fā)現(xiàn)，P. marneffei刺激的DCs能夠活化更多的靜息狀態(tài)的 CD4+ T 細(xì)胞,，為HIV-1感染提供了大量的靶細(xì)胞,。本研究通過(guò)分析機(jī)會(huì)性病原體對(duì)DC-HIV相互作用的影響，加深了對(duì)病毒致病機(jī)理的理解,。
該項(xiàng)目合作單位有昆明醫(yī)學(xué)院第一附屬醫(yī)院等,。研究得到來(lái)自中科院、國(guó)家基金委和上海市等項(xiàng)目的資助,。（生物谷Bioon.com）
doi:10.1371/journal.pone.0027609
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Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection by Activating Primary CD4+ T Cells.
Yan Qin1, Yuye Li2, Wan Liu1, Renrong Tian1,Qianqian Guo1, Shaoyou Li2, Hongbin Li2, Daojun Zhang2, Yongtang Zheng3, Li Wu4, Ke Lan1*, Jianhua Wang1*
Penicillium marneffei (P. marneffei) is considered an indicator pathogen of AIDS, and the endemicity and clinical features of P. marneffei have been described. While, how the co-infection of P. marneffei exacerbate deterioration of the immune response remains poorly understood. Here we isolated P. marneffei from the cutaneous lesions of AIDS patients and analyzed its effects on HIV-1-dendritic cells (DCs) interaction. We demonstrated that the monocyte-derived dendritic cells (MDDCs) could be activated by both thermally dimorphic forms of P. marneffei for significantly promoting HIV-1trans-infection of CD4+ T cells, while these activated MDDCs were refractory to HIV-1 infection. Mechanistically, P. marneffei-activated MDDCs endocytosed large amounts of HIV-1 and sequestrated the internalized viruses into tetrapasnin CD81+ compartments potentially for proteolysis escaping. The activated MDDCs increased expression of intercellular adhesion molecule 1 and facilitated the formation of DC-T-cell conjunctions, where much more viruses were recruited. Moreover, we found that P. marneffei-stimulated MDDCs efficiently activated resting CD4+ T cells and induced more susceptible targets for viral infection. Our findings demonstrate that DC function and its interaction with HIV-1 have been modulated by opportunistic pathogens such as P. marneffei for viral dissemination and infection amplification, highlighting the importance of understanding DC-HIV-1 interaction for viral immunopathogenesis elucidation.
