Inhibition of DC‐SIGN‐mediated trans infection of T cells by mannose‐binding lectin

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Abstract
Summary: Some dendritic cells (DC) express a cell‐surface lectin called ‘dendritic cell‐specific intracellular adhesion molecule 3 (ICAM‐3)‐grabbing non‐integrin’ (DC‐SIGN). DC‐SIGN has been shown to mediate a type of infection called ‘trans’ infection, where DC bind human immunodeficiency virus (HIV) and efficiently transfer the virus to T cells. We investigated the possibility that mannose‐binding lectin (MBL), a soluble lectin that functions as a recognition molecule in innate immunity and that binds to HIV, could block trans infection mediated by DC‐SIGN. Binding studies with glycoprotein (gp)120/gp41‐positive and ‐negative virus preparations suggested that DC‐SIGN and MBL bind primarily to glycans on gp120/gp41, as opposed to glycans on host‐cell‐derived proteins, indicating a close overlap in the binding site of the two lectins and supporting the notion that MBL could prevent binding of HIV to DC‐SIGN. Preincubation of X4, R5 or dual‐tropic HIV strains with MBL prevented DC‐SIGN‐mediated trans infection of T cells. The mechanism of MBL blocking trans infection of T cells was at least partly caused by blocking of virus binding to DC‐SIGN positive cells. This study shows that MBL prevents DC‐SIGN‐mediated trans infection of T cells in vitro and suggests that in infected persons, MBL may inhibit DC‐SIGN‐mediated uptake and spread of HIV.