Differential susceptibility of human thymic dendritic cell subsets to X4 and R5 HIV-1 infection.
OBJECTIVE
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.


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.


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.


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.
Unité de Régulation des Infections Rétrovirales, Institut Pasteur, Paris, France. nathalis@bhcs.com
Nathalie
N
Schmitt
Marie-Thérèse
MT
Nugeyre
Daniel
D
Scott-Algara
Marie-Christine
MC
Cumont
Françoise
F
Barré-Sinoussi
Gianfranco
G
Pancino
Nicole
N
Israël
D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D004198:Disease Susceptibility / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D013950:Thymus Gland / Q000473:pathology / Q000821:virology*; D014779:Virus Replication / Q000502:physiology
D016898:Interferon-alpha; D019713:Receptors, CCR5; D019718:Receptors, CXCR4