期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2104721118
关键词
HIV-1; iNKT cells; ART; gut; immune activation
资金
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-18-2-0040]
- US Department of Defense (DOD) [W81XWH-18-2-0040]
- US National Institute of Allergy and Infectious Diseases [Y1-AI-5026-03]
- Thai Red Cross AIDS Research Centre [RV254]
- Government Pharmaceutical Organization (Thailand)
- Gilead
- Merck
- ViiV Healthcare
This study found that iNKT cells are early targets for HIV-1 infection, leading to their rapid depletion during AHI. The cells in blood had elevated expression of cell death-associated transcripts during untreated AHI, and they showed diminished responsiveness to stimulation early in chronic infection. Moreover, HIV-1 DNA and viral RNA were detected in iNKT cells, suggesting active infection of these cells in vivo.
Acute HIV-1 infection (AHI) results in the widespread depletion of CD4(+) T cells in peripheral blood and gut mucosal tissue. However, the impact on the predominantly CD4(+) immunoregulatory invariant natural killer T (iNKT) cells during AHI remains unknown. Here, iNKT cells from peripheral blood and colonic mucosa were investigated during treated and untreated AHI. iNKT cells in blood were activated and rapidly depleted in untreated AHI. At the time of peak HIV-1 viral load, these cells showed the elevated expression of cell death-associated transcripts compared to preinfection. Residual peripheral iNKT cells suffered a diminished responsiveness to in vitro stimulation early into chronic infection. Additionally, HIV-1 DNA, as well as spliced and unspliced viral RNA, were detected in iNKT cells isolated from blood, indicating the active infection of these cells in vivo. The loss of iNKT cells occurred from Fiebig stage III in the colonic mucosa, and these cells were not restored to normal levels after initiation of ART during AHI. CD4(+) iNKT cells were depleted faster and more profoundly than conventional CD4(+) T cells, and the preferential infection of CD4(+) iNKT cells over conventional CD4(+) T cells was confirmed by in vitro infection experiments. In vitro data also provided evidence of latent infection in iNKT cells. Strikingly, preinfection levels of peripheral blood CD4(+) iNKT cells correlated directly with the peak HIV-1 load. These findings support a model in which iNKT cells are early targets for HIV-1 infection, driving their rapid loss from circulation and colonic mucosa.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据