Diversity of receptors binding HIV on dendritic cell subsets

Abstract

The ability of HIV-1 to use dendritic cells (DCs) for transport and to transfer virus to activated T cells in the lymph node may be crucial in early HIV-1 pathogenesis. We have characterized primary DCs for the receptors involved in viral envelope attachment and observed that C-type lectin receptor (CLR) binding was predominant in skin DCs, whereas binding to emigrating and tonsil DCs was CD4-dependent. No one CLR was solely responsible for envelope binding on all skin DC subsets. DC-SIGN (DC-specific ICAM-3–grabbing nonintegrin) was only expressed by CD14+CDlalo dermal DCs. The mannose receptor was expressed by CD1ahi and CD14+CDlalo dermal DCs, and langerin was expressed by Langerhans cells. The diversity of CLRs able to bind HIV-1 in skin DCs may reflect their ability to bind a range of microbial glycoproteins.

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Figure 1: CD4 and DC-SIGN expression by MDDCs and tissue DCs after collagenase treatment.
Figure 2: Isolation and purification of DC populations and identification by standard markers.
Figure 3: Two patterns of HIV gp120 binding to CD4 and CLRs on multiple DC subsets.
Figure 4: Quantification of HIV gp120 binding on MDDCs, MDLCs and immature and emigrant skin DC subsets.
Figure 5: HIV gp120 binding and MCLR phenotypes of epidermal LC and dermal DC subsets.
Figure 6: HIV gp120 binding on MCLR transfectants.
Figure 7: Expression of CLRs on DC subsets in sections of skin.
Figure 8: Mechanism of entry of infectious HIV into MDDCs or blood DCs.

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Acknowledgements

Supported by the Australian National Centre for HIV Virology Research (A. L. C.); an Australian Postgraduate Award (to S. T.); an Australian National Health and Medical Research Council grant (to P. U. C.); an NIH MSTP grant (to P. U. C.); a Wellcome trust and ANZ trustees grant (to P. U. C.); the Deutsche Forschungsgemeinschaft (S. P.); NIH grants R0140880 and R0135383 (to R. D.); a Burroughs Wellcome Fund translational research award (to R. W. D.); and an Elizabeth Glaser Scientist award from the Pediatric AIDS Foundation (to R. W. D.). Thanks to R. Berkowicz for tonsils, the staff of the VPSU for normal skin, to M. Taylor and D. Hart for cells and reagents and C. Wolczak for processing the manuscript.

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Correspondence to Anthony L. Cunningham.

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Turville, S., Cameron, P., Handley, A. et al. Diversity of receptors binding HIV on dendritic cell subsets. Nat Immunol 3, 975–983 (2002). https://doi.org/10.1038/ni841

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