近日,，國際著名雜志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,，從而有效地增強與CD4+ T細胞的接觸,，增強HIV-1從DCs至T細胞的傳播,；
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最常見AIDS相關聯(lián)的機會性病原體感染性疾病,。機會性病原體如何加速免疫系統(tǒng)的過度激活從而促進AIDS疾病進程,，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下,，與相關單位合作,，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會性病原體對樹突狀細胞（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 細胞，為HIV-1感染提供了大量的靶細胞,。本研究通過分析機會性病原體對DC-HIV相互作用的影響,，加深了對病毒致病機理的理解。
該項目合作單位有昆明醫(yī)學院第一附屬醫(yī)院等,。研究得到來自中科院,、國家基金委和上海市等項目的資助。（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.
