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Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia
In HIV infection, dendritic cells (DCs) may play multiple roles, probably including initial HIV uptake in the anogenital mucosa, transport to lymph nodes, and subsequent transfer to T cells. The effects of HIV-1 on DC maturation are controversial, with several recent conflicting reports in the literature. In this study, microarray studies, confirmed by real-time PCR, demonstrated that the genes encoding DC surface maturation markers were among the most differentially expressed in monocyte-derived dendritic cells (MDDCs), derived from human blood, treated with live or aldrithriol-2-inactivated HIV-1BaL. These effects translated to enhanced cell surface expression of these proteins but differential expression of maturation markers was only partial compared with the effects of a conventional potent maturation stimulus. Such partially mature MDDCs can be converted to fully mature cells by this same potent stimulus. Furthermore, live HIV-1 stimulated greater changes in maturation marker surface expression than aldrithriol-2-inactivated HIV-1 and this enhanced stimulation by live HIV-1 was mediated via CCR5, thus suggesting both viral replication-dependent and -independent mechanisms. These partially mature MDDCs demonstrated enhanced CCR7-mediated migration and are also able to stimulate interacting T cells in a MLR, suggesting DCs harboring HIV-1 might prepare CD4 lymphocytes for transfer of HIV-1. Increased maturation marker surface expression was also demonstrated in native DCs, ex vivo Langerhans cells derived from human skin. Thus, HIV initiates maturation of DCs which could facilitate subsequent enhanced transfer to T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a National Health and Medical Research Council Program Grant ID 358399.
2 Address correspondence and reprint requests to Dr. Anthony L. Cunningham, Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia. E-mail address: tony_cunningham{at}wmi.usyd.edu.au
3 Abbreviations used in this paper: DC, dendritic cell; CLR, C-type lectin receptor; MR, mannose receptor; LC, Langerhans cell; MDDC, monocyte-derived DC; iMDDC, immature MDDC; AT-2, aldrithriol-2; TCID50, 50% tissue culture infectious dose; MOI, multiplicity of infection; β2m, β2-microglobulin.
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