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Dendritic cells sample HIV-1 through an intestinal epithelial cell monolayer

The intestinal mucosa is a preferential portal of entry for HIV-1 during mother-to-child transmission. Oral infection is also a well documented route for transmission of HIV-1 in neonates. Neonates can acquire the disease by breast-feeding, moreover presence of blood in gastric aspirates of neonates born to HIV-1 infected mothers has also been incriminated as a risk factor in the transmission of HIV-1. Multiple mechanisms for mucosal HIV-1 transmission have been proposed, however the exact role played by dendritic cells in facilitating viral passage across intestinal epithelium have not been fully defined. We had hypothesized that sub-mucosal dendritic cells (DCs) can mediate mucosal transmission of HIV-1 through a process similar to bacterial sampling through gastrointestinal epithelium (Rescigno M., Nat.Immun.2001).

An in vitro transwell co-colture system of colonic cell line Caco-2 and DCs was developed. DCs collected on transwell after incubation on the apical side of Caco-2 monolayer with cell-free HIV-1 (R5 and X4 phenotype), were able to transfer infection efficiently to susceptible target cells. Abundant HIV-1 replication (as measured by p24 antigen ELISA until day 25 of DCs-T cells co-culture) was reproducibly observed, suggesting that DCs sampled the virus and transferred it to target cells. DCs retained infection capability for at least 4 days. Confocal microscopy showed intense migration of DCs through the tight junctions of Caco-2, following incubation with HIV-1, at a level comparable to LPS treated cultures (positive control), thus indicating that HIV-1 promotes DCs migration through an epithelial monolayer. This process, already evident after 30 min, reached a peak at 4 h 30 min. GFP-labeled HIV-1 or p24 antigen was detected on the apical side of the Caco-2 monolayer and inside the migrated DCs. Transmission electron microscopy confirmed the localization of HIV-1. Thus, our results show that in the in vitro model DCs migrate through intestinal epithelial cells (IECs) to explore the luminal surface in the presence of HIV-1, are able to uptake the virus and to infect susceptible target cells. The molecular mechanisms underlying HIV-1 induced DCs migration across IECs, and consequent implication for mother-to-child transmission, will be discussed.

Our results clarify the earliest events in the establishment HIV-1 infection at mucosal level and so are of outmost relevance for the development of an effective preventative vaccine.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Cavarelli, M., Foglieni, C., Rescigno, M. et al. Dendritic cells sample HIV-1 through an intestinal epithelial cell monolayer. Retrovirology 6 (Suppl 1), O4 (2009).

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