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Differential susceptibility of human thymic dendritic cell subsets to X4 and R5 HIV-1 infection.
- Source :
-
AIDS (London, England) [AIDS] 2006 Feb 28; Vol. 20 (4), pp. 533-42. - Publication Year :
- 2006
-
Abstract
- Objectives: Human thymus can be infected by HIV-1 with potential consequences on immune regeneration and homeostasis. We previously showed that CD4 thymocytes preferentially replicate CXCR4 tropic (X4) HIV-1 dependently on interleukin (IL)-7. Here we addressed the susceptibility of thymic dendritic cells (DC) to HIV-1 infection.<br />Methods: We investigated the replication ability of CXCR4 or CCR5 (R5) tropic HIV-1 in thymic micro-explants as well as in isolated thymic CD11clowCD14- DC, CD11chighCD14+ DC and plasmacytoid DC subsets.<br />Results: Thymic tissue was productively infected by both X4 and R5 viruses. However, X4 but not R5 HIV-1 replication was enhanced by IL-7 in thymic micro-explants, suggesting that R5 virus replication occurred in cells other than thymocytes. Indeed, we found that R5 HIV-1 replicated efficiently in DC isolated from thymic tissue. The replicative capacity of X4 and R5 viruses differed according to the different DC subsets. R5 but not X4 HIV-1 efficiently replicated in CD11chighCD14+ DC. In contrast, no HIV-1 replication was detected in CD11clowCD14- DC. Both X4 and R5 viruses efficiently replicated in plasmacytoid DC, which secreted interferon-alpha upon HIV-1 exposure. Productive HIV-1 infection also caused DC loss, consistent with different permissivity of each DC subset.<br />Conclusions: Thymic DC sustain high levels of HIV-1 replication. DC might thus be the first target for R5 HIV-1 infection of thymus, acting as a Trojan horse for HIV-1 spread to thymocytes. Furthermore, DC death induced by HIV-1 infection may affect thymopoiesis.
- Subjects :
- Dendritic Cells metabolism
Disease Susceptibility pathology
Disease Susceptibility virology
HIV Infections metabolism
Humans
Interferon-alpha metabolism
Receptors, CCR5 metabolism
Receptors, CXCR4 metabolism
Thymus Gland pathology
Virus Replication physiology
Dendritic Cells virology
HIV Infections virology
HIV-1 physiology
Thymus Gland virology
Subjects
Details
- Language :
- English
- ISSN :
- 0269-9370
- Volume :
- 20
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- AIDS (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 16470117
- Full Text :
- https://doi.org/10.1097/01.aids.0000210607.63138.bc