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

Schmitt, Nathaliea; Nugeyre, Marie-Thérèsea; Scott-Algara, Daniela; Cumont, Marie-Christineb; Barré-Sinoussi, Françoisea; Pancino, Gianfrancoa; Israël, Nicolea,†

doi: 10.1097/01.aids.0000210607.63138.bc
Basic Science

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.

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-α 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.

From the aUnité de Régulation des Infections Rétrovirales, Institut Pasteur, Paris, France

bUnité de Recherche et d'Expertise Physiopathologie des Infections Lentivirales, Institut Pasteur, Paris, France.

Nicole Israel passed away after the submission of this article. We dedicate this publication to her memory.

Received 23 August, 2005

Revised 2 November, 2005

Accepted 6 December, 2005

Correspondence to N. Schmitt/G. Pancino, Unité de Régulation des Infections Rétrovirales, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Tel: +33 1 4568 8738; fax: +33 1 4568 8957 e-mail: nathalis@bhcs.com/gpancino@pasteur.fr

© 2006 Lippincott Williams & Wilkins, Inc.