Surfactant Protein D Binding to Terminal α1-3–Linked Fucose Residues and to Schistosoma mansoni

Abstract

Pulmonary surfactant protein (SP)-D is an important component of the innate immune system of the lung, which is thought to function by binding to specific carbohydrates on the surface of viruses and unicellular pathogens. SP-D has been shown to have a relatively high affinity for the monosaccharides mannose, glucose, and fucose. However, there is limited information on SP-D binding to complex carbohydrate structures, and binding of SP-D to fucose in the context of an oligosaccharide has not yet been investigated. In this study, we used surface plasmon resonance spectroscopy to examine the potential of SP-D to bind to various synthetic fucosylated oligosaccharides, and identified Fucalpha1-3GalNAc and Fucalpha1-3GlcNAc elements as strong ligands. These types of fucosylated glycoconjugates are presented at the surface of Schistosoma mansoni, a parasitic worm that, during development, transiently resides in the lung. In line with the findings by surface plasmon resonance, we found that SP-D can bind to larval stages of S. mansoni, demonstrating for the first time that SP-D interacts with multicellular lung pathogens.

Repeats of LacdiNAc and fucosylated LacdiNAc on N‐glycans of the human parasite Schistosoma mansoni

“…Many carbohydrate epitopes from schistosomes, such as FLDN(F) {Fuc(α1–3)GalNAc(β1–4)[±Fuc(α1–3)]GlcNAc(β1‐)}, LDN(F), and Lewis X, have been shown to be antigenic and several also appear to be targets for the innate immune system through recognition by human lectins [2–5,7,8,19,28–31]. In particular, LDN(F) units, repeats of which are described here, have been shown to be target of the host immune response in schistosomiasis [19,29,38,39].…”

An Insight into the Diverse Roles of Surfactant Proteins, SP-A and SP-D in Innate and Adaptive Immunity

“…In a study involving SP-A −/− and wild-type mice and an intranasal C. neoformans infection model, it was found that disease progression was not influenced by SP-A (Giles et al, 2007). Both encapsulated and acapsular Cryptococci can bind SP-D, but SP-D showed the highest affinity and aggregation for acapsular C. neoformans (van de Wetering et al, 2004a). The ligands for SP-D were identified as capsular components glucuronoxylomannan (GXM) and mannoprotein 1 (MP1) (van de Wetering et al, 2004a).…”

“…Both encapsulated and acapsular Cryptococci can bind SP-D, but SP-D showed the highest affinity and aggregation for acapsular C. neoformans (van de Wetering et al, 2004a). The ligands for SP-D were identified as capsular components glucuronoxylomannan (GXM) and mannoprotein 1 (MP1) (van de Wetering et al, 2004a).…”

“…Their primary structure is organized into a variety of microbes (viruses, bacteria, yeast, and fungi), thus acting as opsonins and having direct and indirect biological effects (Crouch, 2000;Lawson and Reid, 2000;Crouch and Wright, 2001;Shepherd, 2002; Tables 1 and 2). There is one report of SP-D binding to the parasite Schistosoma mansoni (van de Wetering et al, 2004b). SP-A and SP-D bind and/or agglutinate a wide range of microbes that enhance their attachment to phagocytic cells and can lead to killing and enhanced clearance.…”

Levels of complexity in pathogen recognition by C-type lectins

“…Despite the fact that this soluble CLR is a key component of the innate immunity in lung alveoli, limited information is available on its binding to complex carbohydrate structures. Recently, by using surface plasmon resonance spectroscopy, van de Wetering et al [13] identified terminal a1-3-linked fucose residues as strong ligands for SP-D. Furthermore, for the first time, SP-D was shown to bind multicellular larval stages of the parasitic worm Schistosoma mansoni, transiently residing in the lung, by interacting with these fucosylated glycans exposed at the cell surface [13].…”