PLoS One:马尔尼菲青霉菌（P. marneffei)的感染与AIDS研究新进展

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深部真菌马尔尼菲青霉菌（P. marneffei)的感染，已成为继肺结核杆菌和隐球菌外第三个最常见AIDS相关联的机会性病原体感染性疾病。机会性病原体如何加速免疫系统的过度激活从而促进AIDS疾病进程，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华研究员的指导下，与相关单位合作，从P. marneffei与HIV-1共感染的病人皮肤损伤组织中分离出这一具有温度双相的真菌，以其为代表分析了机会性病原体对树突状细胞（Dendritic Cell, DC)与HIV-1相互作用的影响。研究发现，P. marneffei刺激的DCs增加其表面黏附分子ICAM-1的表达，从而有效地增强与CD4+ T细胞的接触，增强HIV-1从DCs至T细胞的传播；另外发现，P. marneffei刺激的DCs能够活化更多的静息状态的 CD4+ T 细胞，为HIV-1感染提供了大量的靶细胞。本研究通过分析机会性病原体对DC-HIV相互作用的影响，加深了对病毒致病机理的理解。

2011年11月，该研究结果在线发表于《PLoS ONE》。该项目合作单位有昆明医学院第一附属医院等。研究得到来自中科院、国家基金委和上海市等项目的资助。

转自http://www.shanghaipasteur.cas.c ... 111208_3409901.html

PLoS One. 2011;6(11):e27609. Epub 2011 Nov 16.
Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection by Activating Primary CD4 T Cells.

Abstract
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-1 trans-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.