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标题：Preferential and persistent impact of acute HIV-1 infection on CD4 ⁺ iNKT cells in colonic mucosa
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作者：Dominic Paquin-Proulx ; Kerri G. Lal ; Yuwadee Phuang-Ngern 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：46
DOI：10.1073/pnas.2104721118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Evidence suggests that HIV-1 disease progression is determined in the early stages of infection. Here, preinfection invariant natural killer T (iNKT) cell levels were predictive of the peak viral load during acute HIV-1 infection (AHI). Furthermore, iNKT cells were preferentially lost in AHI. This was particularly striking in the colonic mucosa, where iNKT cells were depleted more profoundly than conventional CD4 + T cells. The initiation of antiretroviral therapy during AHI-prevented iNKT cell dysregulation in peripheral blood but not in the colonic mucosa. Overall, our results support a model in which iNKT cells are early and preferential targets for HIV-1 infection during AHI. 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.
关键词：HIV-1; iNKT cells; ART; gut; immune activation