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Preferential and persistent impact of acute HIV-1 infection on CD4 + iNKT cells in colonic mucosa.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Nov 16; Vol. 118 (46). - Publication Year :
- 2021
-
Abstract
- Acute HIV-1 infection (AHI) results in the widespread depletion of CD4 <superscript>+</superscript> T cells in peripheral blood and gut mucosal tissue. However, the impact on the predominantly CD4 <superscript>+</superscript> 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 <superscript>+</superscript> iNKT cells were depleted faster and more profoundly than conventional CD4 <superscript>+</superscript> T cells, and the preferential infection of CD4 <superscript>+</superscript> iNKT cells over conventional CD4 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br />Competing Interests: Competing interest statement: J.A. previously received honoraria from Merck, ViiV Healthcare, Roche, AbbVie, and Gilead for her participation in advisory meetings.<br /> (Copyright © 2021 the Author(s). Published by PNAS.)
- Subjects :
- Adolescent
Adult
Disease Progression
Female
HIV Infections virology
HIV-1 immunology
Humans
Male
Middle Aged
Persistent Infection immunology
Persistent Infection virology
Young Adult
CD4-Positive T-Lymphocytes immunology
Colon immunology
Colon virology
HIV Infections immunology
Intestinal Mucosa immunology
Intestinal Mucosa virology
Natural Killer T-Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 118
- Issue :
- 46
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 34753817
- Full Text :
- https://doi.org/10.1073/pnas.2104721118