In Vitro Derived Dendritic Cells trans-Infect CD4 T Cells Primarily with Surface-Bound HIV-1 Virions

King's College London, United Kingdom
PLoS Pathogens (Impact Factor: 7.56). 02/2007; 3(1):e4. DOI: 10.1371/journal.ppat.0030004
Source: PubMed


Author Summary
Dendritic cells (DCs) patrol peripheral mucosal sites, capturing and processing potential pathogens into antigenic peptides for presentation to T cells of lymphoid organs, and thereby initiating an immune response. HIV-1 had been proposed to use DCs as “Trojan horses,” hiding inside the DCs and surviving the degradation pathway to gain access to the lymph nodes and spread to the T cells. Our study challenges this “Trojan horse” model by showing that only HIV-1 virions bound to the surface of DCs, and not internalized virions, are transmitted to T cells. Even when T cells specifically recognized the antigen presented by DCs, the infection of T cells was principally mediated by virions remaining at the surface of the DCs. Interestingly, in this context of antigen-specific recognition, which increases the trafficking toward the immunological synapse of DC internal vesicles, where HIV-1 virions seem to hide, a few internal virions could infect T cells. Our findings suggest that in vivo transmission to T cells of HIV-1 virions captured by DCs should be more sensitive to neutralization than previously expected.

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Available from: Marielle Cavrois
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    • "Additionally, the data also suggests that the compartment may be intracellular with no access to the extracellular space, rendering it trypsin-resistant. Cavrois et al., recently performed a study in dendritic cells to demonstrate that trans-infection occurred primarily by surface-accessible HIV-1 and suggested that internalized HIV does not play a role in trans-infection [46]. This finding somewhat contradicts that of our own, but may be explained due to the different model and cell type used. "
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    • "Each lectin receptor appears to have a unique and distinct function. HIV-1 transfer in trans, through the capture of virus by a CLR, such as DC-SIGN, occurs early in in vitro experiments (Cavrois et al., 2007; Dong et al., 2007; Izquierdo-Useros et al., 2007), and is designated trans-infection. However, DC lectin receptors are important molecules involved in the presentation of foreign antigens. "
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