Retinoic acid imprints a mucosal-like phenotype on dendritic cells with an increased ability to fuel HIV-1 infection.
Retinoic acid imprints a mucosal-like phenotype on dendritic cells with an increased ability to fuel HIV-1 infection.
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DOI：
10.4049/jimmunol.1402623
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发表时间：
2015-03-01
期刊：
影响因子：
--
通讯作者：
Martinelli E
中科院分区：
文献类型：
--
作者：
Guerra-Pérez N;Frank I;Veglia F;Aravantinou M;Goode D;Blanchard JL;Gettie A;Robbiani M;Martinelli E
组织微环境塑造了树突状细胞（DC）的特征和功能，树突状细胞是HIV感染和传播的重要参与者。值得注意的是，肠道中的DC具有协调免疫应答和耐受性之间的平衡的艰巨任务。它们产生视黄酸（RA），其印记肠道归巢表型并影响周围的DC。为了研究肠道微环境如何影响DC驱动HIV感染的能力，我们用RA（RA-DC）调节人未成熟单核细胞衍生的DC（moDC），然后用HIV对其进行脉冲并将其与自体T细胞混合。RA-DCs表现为半成熟的粘膜样表型，并释放较高量的TGF-β1和CCL 2。使用流式细胞术、蛋白质印迹和显微镜，我们确定moDCs表达细胞粘附分子MAdCAM-1，并且RA增加其表达。MAdCAM-1也在恒河猴（Macaca mulata）肠系膜淋巴结中的一小部分DC上检测到。与moDC相比，RA-DC形成更多的DC-T细胞缀合物，并在DC-T细胞混合物中促进显著更高的HIV复制。这与MAdCAM-1表达的增加相关。阻断MAdCAM-1可部分抑制增强的HIV复制。总之，RA影响DC表型，增加其加剧HIV感染的能力。我们描述了一种以前未知的机制，可能有助于HIV在肠道中的快速传播，肠道是粘膜暴露后HIV复制的主要场所。
The tissue microenvironment shapes the characteristics and functions of dendritic cells (DCs), which are important players in HIV infection and dissemination. Notably, DCs in the gut have the daunting task of orchestrating the balance between immune response and tolerance. They produce retinoic acid (RA), which imprints a gut homing phenotype and influences surrounding DCs. To investigate how the gut microenvironment impacts the ability of DCs to drive HIV infection, we conditioned human immature monocyte derived DCs (moDCs) with RA (RA-DCs), before pulsing them with HIV and mixing them with autologous T cells. RA-DCs showed a semi-mature, mucosal-like phenotype and released higher amounts of TGF-β1 and CCL2. Using flow cytometry, western blot and microscopy, we determined that moDCs express the cell adhesion molecule MAdCAM-1 and that RA increases its expression. MAdCAM-1 was also detected on a small population of DCs in rhesus macaque (Macaca mulata) mesenteric lymph node. RA-DCs formed more DC-T cell conjugates and promoted significantly higher HIV replication in DC-T cell mixtures compared to moDCs. This correlated with the increase in MAdCAM-1 expression. Blocking MAdCAM-1 partially inhibited the enhanced HIV replication. In summary, RA influences DC phenotype increasing their ability to exacerbate HIV infection. We describe a previously unknown mechanism that may contribute to rapid HIV spread in the gut, a major site of HIV replication after mucosal exposure.
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影响因子：
32.4
作者：
Hall JA;Cannons JL;Grainger JR;Dos Santos LM;Hand TW;Naik S;Wohlfert EA;Chou DB;Oldenhove G;Robinson M;Grigg ME;Kastenmayer R;Schwartzberg PL;Belkaid Y
通讯作者：
Belkaid Y
影响因子：
17.1
作者：
Amarnath S;Mangus CW;Wang JC;Wei F;He A;Kapoor V;Foley JE;Massey PR;Felizardo TC;Riley JL;Levine BL;June CH;Medin JA;Fowler DH
通讯作者：
Fowler DH
影响因子：
24.5
作者：
Iliev, I. D.;Spadoni, I.;Rescigno, M.
通讯作者：
Rescigno, M.
影响因子：
4.1
作者：
Derby, Nina;Martinelli, Elena;Robbiani, Melissa
通讯作者：
Robbiani, Melissa
DOI：
10.1073/pnas.0911796106
发表时间：
2009-12-08
影响因子：
11.1
作者：
Cicala, Claudia;Martinelli, Elena;Arthos, James
通讯作者：
Arthos, James