Impaired pro-inflammatory cytokine production and increased Th2-biasing ability of dendritic cells exposed to Taenia excreted/secreted antigens: A critical role for carbohydrates but not for STAT6 signaling César A. Terrazas a , Lorena Gómez-García b , Luis I. Terrazas a, * a Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico b Departamento de Inmunología, Instituto Nacional de Cardiología, México, D.F., Mexico article info Article history: Received 2 January 2010 Received in revised form 23 February 2010 Accepted 24 February 2010 Keywords: Taenia crassiceps Dendritic cells Excreted/secreted helminth antigens Modulation of immune response abstract In cysticercosis, a parasitic disease caused by cestodes, the details of early interactions between parasite antigens and innate cells from the host are not well understood. In this study, the role of cestode-condi- tioned dendritic cells (DCs) in priming Th1 versus Th2 responses to bystander antigen was examined by using CD11c + DCs as antigen-presenting cells and naive CD4 + DO11.10 lymphocytes specific to ovalbumin (OVA) as responding cells. No conventional maturation was induced in DCs exposed to Taenia crassiceps excreted/secreted antigens (TcES). The ability of TcES to affect Toll-like receptor (TLR)-mediated matura- tion and the pro-inflammatory response was analyzed by co-pulsing DCs with TcES and TLR ligands. DCs exposed to TcES blocked TLR4, TLR9 and Toxoplasma soluble antigen-induced phenotypic maturation. TcES-exposed DCs also blocked secretion of pro-inflammatory cytokines and alloreactive T cell prolifer- ation, while preserving IL-10 production. DCs pulsed with TcES + OVA suppressed IFN-c, whereas they induced greater IL-4 production by CD4 + DO11.10 cells. TcES with chemically-altered glycans failed to modulate TLR-mediated activation of DCs and their Th1-inhibitng ability, which was STAT6-independent. Our results reflect the capacity of TcES glyco-antigens to modulate Th1-type and inflammatory responses mediated through DC activation. Ó 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Helminths and their antigens are now recognized as possessing important immunomodulatory activities, but how helminth infec- tions cause these immuno-regulatory events remains unclear (Maizels and Yazdanbakhsh, 2003). A key feature of helminth infections is the induction of Th2-biased immune responses in their hosts (Maizels and Yazdanbakhsh, 2003; Maizels et al., 2004), where antigen-presenting cells (APCs) may play an impor- tant role in this process (MacDonald and Maizels, 2008). Pattern recognition receptors (PRRs) of dendritic cells (DCs) recognize and bind to conserved pathogen motifs such as lipopolysaccharide (LPS) in Gram-negative bacteria, flagellin, RNA of viruses and sev- eral molecules in intracellular protozoa (Akira and Takeda, 2004), including cyclophilin from Toxoplasma gondii (Aliberti et al., 2003) and glycoinositolphospholipids (GIPL) from Trypanosoma cruzi (Brodskyn et al., 2002). Among PRRs, the Toll-like receptor (TLR) family is the main group of receptors known to be involved in maturation and induction of inflammatory cytokines in DCs (Akira and Takeda, 2004). Most of the currently known pathogen molecules recognized by TLRs are primarily found in intracellular pathogens capable of instructing DCs to release pro-inflammatory cytokines and drive Th1 responses (Akira and Takeda, 2004). In contrast, the results of interactions between helminths and the in- nate immune system are not well understood. However, some ad- vances in this area indicating that helminth extracts may instruct Th2 responses have been reached through studies on nematodes (Holland et al., 2000; Whelan et al., 2000; Pinelli et al., 2007) and trematodes (Pearce et al., 2004), whereas the interactions of ces- tode antigens with the innate immune system and their role in Th2 polarization has been largely neglected (Maizels, 2009). We have investigated the immunomodulatory activities of the cestode Taenia crassiceps, which as in most helminth infections in- duces Th2-type biased immune responses (Villa and Kuhn, 1996; Terrazas et al., 1998; Toenjes et al., 1999) as well as an important anergy of splenocytes in response to both antigen-specific and polyclonal stimuli (Sciutto et al., 1995; Villa and Kuhn, 1996; Rodriguez-Sosa et al., 2003, 2004). Moreover, altered susceptibility has been observed when T. crassiceps-infected mice were co- infected with T. cruzi (Rodriguez et al., 1999), a virus (Spolski 0020-7519/$36.00 Ó 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijpara.2010.02.016 * Corresponding author. Address: Unidad de Biomedicina, FES-Iztacala, Univers- idad Nacional Autónoma de México, Av. De los Barrios # 1, Los Reyes Iztacala, 54090 Tlalnepantla, Edo. de México, Mexico. Tel.: +52 55 5623 1333x39794; fax: +52 55 5623 1138. E-mail address: literrazas@campus.iztacala.unam.mx (L.I. Terrazas). International Journal for Parasitology 40 (2010) 1051–1062 Contents lists available at ScienceDirect International Journal for Parasitology journal homepage: www.elsevier.com/locate/ijpara