The Open Vaccine Journal, 2010, 3, 1-6 1 1875-0354/10 2010 Bentham Open Open Access The Mannose-Binding Protein Sm60 from Schistosoma mansoni Suppresses T Cell Proliferation via Inhibition of Interleukin-2 Production Arlete A. M. Coelho-Castelo 1, * , Ademilson Panunto-Castelo 2 , Alan Berlese 1 , João S. Silva 1 and Vanderlei Rodrigues 1 1 Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil 2 Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil Abstract: Adult worms of Schistosoma mansoni live in the bloodstream, employing immune evasion strategies and exposing few antigens to the immune system. The tegumental surface of adult worms presents Sm60, a mannose-binding protein, which induces neutrophil migration and mast cell degranulation. Here we demonstrated that Sm60 is able to block the in vitro antigen-specific or polyclonal spleen cell proliferation induced by keyhole limpet haemocyanin (KLH) or con- canavalin A (Con A), respectively. To address the mechanism of inhibition, we evaluated some cytokines in culture and observed that Sm60 decreased significantly the synthesis of interleukin (IL)-2 induced in response to KLH, but not other cytokines. To block the suppression triggered by Sm60, exogenous IL-2 or α-methyl-mannoside were added to KLH- stimulated cultures pulsed with Sm60. Only IL-2 abolished the Sm60 effect, suggesting that Sm60 blocked the lymphop- roliferation through the inhibition of IL-2 production, in a carbohydrate recognition domain (CRD)-independent mecha- nism. Our results suggest that Sm60 could participate in the immune evasion mechanisms of S. mansoni. Keywords: Schistosoma mansoni, Antigen, Lectin, Sm60, Immunosuppression, Interleukin-2. INTRODUCTION Schistosomiasis is one of the major health problems in 74 developing countries, afflicting at least 200 million people. Another 600 million people are at risk of infection [1]. The etiologic agents, which are trematodes of the genus Schisto- soma, establish chronic infections in their hosts in spite of the presence of specific cellular and humoral immune re- sponses. These parasites have evolved a number of immune evasion mechanisms to live in the vasculature of the host, such as shedding of tegument membrane, acquisition of host products onto the tegument to mask its foreign status, mo- lecular mimicry and host immune response inhibitor factors [2]. Lectins are proteins that bind carbohydrates reversibly and with high specificity. They are not enzymatically active on the sugars and are not antibodies but have the ability to recognise molecules inside cells, on cell surfaces, and in physiological fluids [3, 4]. The wide distribution of lectins among living beings suggests that lectins have important physiological functions. In addition, the great diversity of these proteins regarding structure, carbohydrate-binding specificity and distribution indicates that they may have evolved a variety of distinct roles in different organisms [3-6]. In infection, after the first indication that influenza virus haemagglutinin is responsible for the attachment of *Address correspondence to this author at the Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, USP, Av. Bandei- rantes 3900. 14049-900, Ribeirão Preto, SP, Brazil; Tel: 55-16-3602-4538; Fax: 55-16-3633-6631; E-mail: arlete@fmrp.usp.br the virus to the host cells as a prerequisite for infection, mainly by Alfred Gottschalk in the 1950s [6], many reports have demonstrated that lectins from mammals and several pathogens can have an important function in the infection process [4]. With reference to helminths, there has been little work on the identification and characterization of their lectins. In tre- matodes, lectin activity has been described in cercarial pene- tration glands of the avian schistosomes Trichobilharzia szi- dati and T. regenti [7, 8], and fish schistosome Diplostomum pseudospathaceum [9]. The lectin-like protein from D. pseu- dospathaceum was recently isolated from penetration glands by affinity chromatography with a size of ~24-kDa, strongly basic nature and both lectin and enzyme activities [10]. Con- cerning human schistosomes, Trottein et al. suggested that S. mansoni displays selectin-like properties with affinity for the sialyl Lewis X (Le x ) oligosaccharides, providing new in- sights into the biologic roles of selectins and Le x -related structures in immunity against helminth parasites [11]. Previously we reported the isolation and characterisation of a D-mannose-binding protein, termed Sm60, from S. man- soni tegument. This lectin-like protein was recovered in the mannose-eluted fraction upon affinity chromatography on immobilised mannose of the soluble antigen fraction from adult worm tegument and cercariae. When analysed by SDS- PAGE and isoelectrofocusing, Sm60 was detected as a prominent doublet with an apparent molecular mass of 60/66-kDa and as a single band with a pI of 6.9, respectively. In addition to adult worms, Sm60 was also recognized in preparations of schistosomula extract and soluble egg anti-