Surfactant Protein D Modulates HIV Infection of Both T-Cells and Dendritic Cells

Jens Madsen,Nades Palaniyar,Howard W Clark,Daniel A Mitchell,Tao Dong,Gaurav D Gaiha

doi:10.1371/journal.pone.0059047

Abstract

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo.

Highlights

Surfactant protein D (SP-D) is a secreted soluble C-type lectin with a collagenous domain belonging to the group termed collectins [1]
Surfactant Protein D (SP-D) bound to immobilized BaL Human immunodeficiency virus (HIV) particles in the presence of CaCl2, but the binding was inhibited by both mannose and EDTA, suggesting involvement of the Ctype lectin CRD (Figure 1A)
To verify the interaction between SP-D and HIV using another methodology, we further investigated the nature of the SP-D binding to HIV by surface plasmon resonance

Summary

Introduction

Surfactant protein D (SP-D) is a secreted soluble C-type lectin with a collagenous domain belonging to the group termed collectins [1]. Each chain has four domains: 1) a N-terminal region with cysteine residues involved in the higher oligomerisation of the mature SP-D molecule; 2) a collagen like region with hydroxylated lysine and proline residues; 3) an a-helical coiled-coil neck region where the initial trimeric unit formation is initiated and 4) a calcium-dependent carbohydrate recognition domain (CRD) at the C-terminus that is conserved across species [2]. The mature SP-D protein is oligomerized into a dodecameric molecule with four trimeric units that come together involving the N-terminal region with two cysteine residues in each poly peptidechain [3,4]. This collectin family includes other members such as surfactant protein A (SP-A) and mannose binding lectin (MBL). SP-D promotes agglutination and phagocytosis of micro organisms [5,6], has a chemotactic effect on phagocytes [7,8], modulates inflammatory responses [6,9,10], has a direct anti-microbial effect [11,12] and has been shown in in vivo models to be involved in the response to and clearance of viruses such as influenza A virus (IAV) and respiratory syncytial virus (RSV) [13,14,15]

Methods

Results

Conclusion