Intestinal endothelial cells increase HIV infection and latency in resting and activated CD4 + T cells, particularly affecting CCR6 + CD4 + T cells.
Intestinal endothelial cells increase HIV infection and latency in resting and activated CD4 + T cells, particularly affecting CCR6 + CD4 + T cells.
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DOI：
10.1186/s12977-023-00621-y
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发表时间：
2023-05-18
期刊：
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
--
作者：
通过抑制性抗逆转录病毒治疗，大多数患者的艾滋病毒感染得到了很好的控制。然而，由于CD 4 + T细胞中的潜伏病毒储库，特别是在淋巴组织环境中，包括肠道相关淋巴组织，根除和治愈仍然遥不可及。在HIV患者中，存在T辅助细胞的广泛耗竭，特别是来自肠粘膜区域的T辅助细胞17，并且肠道是最大的病毒储存场所之一。内皮细胞排列在淋巴管和血管中，在以前的研究中发现它们促进HIV感染和潜伏期。在这项研究中，我们研究了肠粘膜区的内皮细胞-肠内皮细胞-对HIV感染和T辅助细胞潜伏期的影响。我们发现，肠道内皮细胞显着增加生产和潜伏的HIV感染的休息CD 4 + T辅助细胞。在活化的CD 4 + T细胞中，内皮细胞除了增加生产性感染外，还能够形成潜伏感染。内皮细胞介导的HIV感染在记忆T细胞中比幼稚T细胞更突出，并且它涉及细胞因子IL-6，但不涉及共刺激分子CD 2。CCR 6 + T辅助细胞17亚群对这种内皮细胞促进的感染特别敏感。内皮细胞广泛存在于包括肠粘膜区域在内的淋巴组织中，并在生理上定期与T细胞相互作用，显著增加HIV感染和CD 4 + T细胞中的潜伏储库形成，特别是在CCR 6 + T辅助细胞17中。我们的研究强调了内皮细胞和淋巴组织环境在HIV病理学和持久性中的重要性。
With suppressive antiretroviral therapy, HIV infection is well-managed in most patients. However, eradication and cure are still beyond reach due to latent viral reservoirs in CD4 + T cells, particularly in lymphoid tissue environments including the gut associated lymphatic tissues. In HIV patients, there is extensive depletion of T helper cells, particularly T helper 17 cells from the intestinal mucosal area, and the gut is one of the largest viral reservoir sites. Endothelial cells line lymphatic and blood vessels and were found to promote HIV infection and latency in previous studies. In this study, we examined endothelial cells specific to the gut mucosal area—intestinal endothelial cells—for their impact on HIV infection and latency in T helper cells. We found that intestinal endothelial cells dramatically increased productive and latent HIV infection in resting CD4 + T helper cells. In activated CD4 + T cells, endothelial cells enabled the formation of latent infection in addition to the increase of productive infection. Endothelial-cell-mediated HIV infection was more prominent in memory T cells than naïve T cells, and it involved the cytokine IL-6 but did not involve the co-stimulatory molecule CD2. The CCR6 + T helper 17 subpopulation was particularly susceptible to such endothelial-cell-promoted infection. Endothelial cells, which are widely present in lymphoid tissues including the intestinal mucosal area and interact regularly with T cells physiologically, significantly increase HIV infection and latent reservoir formation in CD4 + T cells, particularly in CCR6 + T helper 17 cells. Our study highlighted the importance of endothelial cells and the lymphoid tissue environment in HIV pathology and persistence.
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影响因子：
4.8
作者：
Schilthuis M;Verkaik S;Walhof M;Philipose A;Harlow O;Kamp D;Kim BR;Shen A
通讯作者：
Shen A
影响因子：
6.7
作者：
Chavez L;Calvanese V;Verdin E
通讯作者：
Verdin E
DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
DOI：
10.1073/pnas.94.24.13193
发表时间：
1997-11-25
影响因子：
11.1
作者：
Chun, TW;Stuyver, L;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
4.4
作者：
Kim, Connie J.;McKinnon, Lyle R.;Kaul, Rupert
通讯作者：
Kaul, Rupert