Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin mediates HIV-1 infection of and transmission by M2a-polarized macrophages in vitro
Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin mediates HIV-1 infection of and transmission by M2a-polarized macrophages in vitro
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DOI：
10.1097/qad.0b013e32835cfc82
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发表时间：
2013-03-13
期刊：
影响因子：
3.8
通讯作者：
Poli, Guido
中科院分区：
文献类型：
--
作者：
Cassol, Edana;Cassetta, Luca;Poli, Guido
目的：评估单核细胞源性巨噬细胞（MDM）向M1和M2a细胞极化对HIV-1复制和传播的体外影响，为巨噬细胞极化在体内的潜在重要性提供新的认识。设计：将人外周血单核细胞分化为MDM 7 d。对照和MDM极化为M1或M2a细胞暴露于不同的HIV-1毒株，并评估其结合和传播病毒到CD4(+) T淋巴细胞的能力。方法：将MDM与肿瘤坏死因子- α (tnf - α)和干扰素- γ (ifn - γ)或白细胞介素-4 （IL-4）孵育18 h，分别获得M1或M2a细胞。通过流式细胞术评估细胞表面抗原的表达，包括CD4和树突状细胞特异性细胞间粘附分子-3捕获非整合素（DC-SIGN）。C-C趋化因子受体5型（CCR5）依赖（R5） HIV-1结合、DNA合成和病毒复制在存在或不存在抗dc - sign阻断单抗的情况下进行评估。还研究了C-X-C趋化因子受体4型（CXCR4）依赖性（X4）和R5 HIV-1从MDM到IL-2激活的CD4(+) T细胞的传递。结果：与对照组相比，DC-SIGN在M2a-MDM上表达显著上调，在M1-MDM上表达下调。DC-SIGN促进了HIV-1在M2a-MDM中的进入和DNA合成，弥补了它们低水平的CD4细胞表达。M2a-MDM以dc - sign依赖的方式有效地将R5和X4 HIV-1传播到CD4(+) T细胞。结论：DC-SIGN促进HIV-1感染M2a-MDM，并促进HIV-1从M2a-MDM向CD4(+) T细胞转移。m2a极化组织巨噬细胞可能在粘膜组织和胎盘中HIV-1的捕获和传播中发挥重要作用。(C) 2013 Wolters Kluwer Health纵向bar， Lippincott Williams & Wilkins AIDS, 2013,27 (7):707-716
Objective: To assess in-vitro effects of monocyte-derived macrophage (MDM) polarization into M1 and M2a cells on HIV-1 replication and transmission and obtain new insights into the potential importance of macrophage polarization in vivo.Design: Human peripheral blood monocytes were differentiated into MDM for 7 days. Control and MDM polarized into M1 or M2a cells were exposed to different strains of HIV-1 and assessed for their ability to bind and transmit virus to CD4(+) T lymphocytes.Methods: MDM were incubated with either tumour necrosis factor-alpha (TNF-alpha) along with interferon-gamma (IFN-gamma) or with interleukin-4 (IL-4) for 18 h to obtain M1 or M2a cells, respectively. Expression of cell surface antigens, including CD4 and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN), was evaluated by flow cytometry. C-C chemokine receptor type 5 (CCR5)-dependent (R5) HIV-1 binding, DNA synthesis and viral replication were assessed in the presence or absence of anti-DC-SIGN blocking mAbs. Transmission of C-X-C chemokine receptor type 4 (CXCR4)-dependent (X4) and R5 HIV-1 from MDM to IL-2 activated CD4(+) T cells was also investigated.Results: DC-SIGN was strongly upregulated on M2a-MDM and downregulated on M1-MDM compared with control MDM. DC-SIGN facilitated HIV-1 entry and DNA synthesis in M2a-MDM, compensating for their low levels of CD4 cell expression. M2a-MDM efficiently transmitted both R5 and X4 HIV-1 to CD4(+) T cells in a DC-SIGN-dependent manner.Conclusion: DC-SIGN facilitates HIV-1 infection of M2a-MDM, and HIV-1 transfer from M2a-MDM to CD4(+) T cells. M2a-polarized tissue macrophages may play an important role in the capture and spread of HIV-1 in mucosal tissues and placenta. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:707-716