Penicillium marneffei-stimulated dendritic cells enhance HIV-1 trans-infection and promote viral infection by activating primary CD4+ T cells.
Penicillium marneffei-stimulated dendritic cells enhance HIV-1 trans-infection and promote viral infection by activating primary CD4+ T cells.
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DOI：
10.1371/journal.pone.0027609
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Qin Y;Li Y;Liu W;Tian R;Guo Q;Li S;Li H;Zhang D;Zheng Y;Wu L;Lan K;Wang J
马尔尼菲青霉（P. marneffei）被认为是艾滋病的指示性病原体，并描述了马尔尼菲青霉的地方性和临床特征。然而，马尔尼菲氏杆菌的联合感染如何加剧免疫反应的恶化仍然知之甚少。在此，我们从艾滋病患者的皮肤病变中分离出P. marneffi，并分析了其对hiv -1树突状细胞（DCs）相互作用的影响。我们证明单核细胞衍生的树突状细胞（mddc）可以被两种热二态形式的马尼菲疟原虫激活，从而显著促进CD4+ T细胞的HIV-1转感染，而这些激活的mddc对HIV-1感染是不耐受的。从机制上讲，P. marneffei激活的mddc内吞大量HIV-1，并将内化的病毒隔离到tetrapasnin CD81+室中，可能用于蛋白水解逃逸。活化的mddc增加了细胞间粘附分子1的表达，促进了dc - t细胞连接的形成，从而招募了更多的病毒。此外，我们发现P. marneffi刺激的mddc有效地激活了静息CD4+ T细胞，并诱导了更敏感的病毒感染靶点。我们的研究结果表明，DC功能及其与HIV-1的相互作用已被机会致病菌（如P. marneffi）调节，以进行病毒传播和感染扩增，这突出了了解DC-HIV-1相互作用对阐明病毒免疫发病机制的重要性。
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.
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