Veterinary Immunology and Immunopathology 148 (2012) 284–292 Contents lists available at SciVerse ScienceDirect Veterinary Immunology and Immunopathology j o ur nal ho me p age: w ww.elsevier.com/locate/vetimm Research paper The response of monocyte derived dendritic cells following exposure to a nematode larval carbohydrate antigen A. Pernthaner ∗ , S.J. Stasiuk 1 , J.M. Roberts, I.A. Sutherland AgResearch, The Hopkirk Research Institute, Grasslands Research Centre, Palmerston North 4442, New Zealand a r t i c l e i n f o Article history: Received 23 April 2012 Received in revised form 8 June 2012 Accepted 30 June 2012 Keywords: CarLA Glycolipid Parasitic nematode Dendritic cells a b s t r a c t The glycolipid CarLA (carbohydrate larval antigen) is present on the epicuticle of the infective-stage larvae of gastrointestinal nematode parasites infecting livestock. The molecule is lost from the surface of the larvae in the few days post-ingestion by a host animal, and the resulting anti-CarLA antibody response has been demonstrated to be pro- tective in vivo. Both the anti-CarLA response, and anti-parasite immunity in general, are slow to develop, and several months of natural exposure to ingested larvae is required. The current study was designed to provide information on how the anti-CarLA response devel- ops, and focuses on the initial recognition of the molecule by human monocyte derived dendritic cells (mdDC) in vitro. Immunofluorescence and flow cytometry demonstrated that mdDC recognise and inter- nalise both the purified and the native form of CarLA, in the case of the latter once it is shed from the larval surface. However, the recognition of CarLA did not result in classical maturation of DC, while there was only transient or minor up-regulation of CD86, CD83, HLA-DR and CD40. Exposure of mdDC to purified CarLA resulted in the increased production of the pro- inflammatory cytokines IL-6 and to a lesser extent of IL-8 and TNF-, and a reduced production of the anti-inflammatory cytokine IL-1RA. CarLA therefore has little ability to mature and functionally alter monocyte derived dendritic cell function. © 2012 Elsevier B.V. All rights reserved. Abbreviations: CarLA, carbohydrate larval antigen; mdDC, monocyte derived dendritic cells; L3, third stage larvae; L4, fourth stage larvae; TcES, Trichostrongylus colubriformis excretory/secretory antigen; TcL3, T. colubriformis third stage larvae; IL-1RA, IL-1 receptor antagonist; IP-10, interferon gamma-induced protein 10; CCL22, chemokine (C–C motif) ligand 22; CLR, C-type lectin receptor; SEA, Schistosoma egg antigen; rh, recombinant human. ∗ Corresponding author at: AgResearch Ltd., The Hopkirk Research Institute, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North 4442, New Zealand. Tel.: +64 6 351 8644; fax: +64 6 351 7853. E-mail address: Tony.Pernthaner@agreserach.co.nz (A. Pernthaner). 1 Current address: University of Calgary, Department of Comparative Biology and Experimental Medicine, Calgary, Alberta, Canada, T2N 4N1. 1. Introduction Long-term chronic infection is characteristic of many parasitic helminth infections in mammals. This can be partly attributed to an ability of the worm to evade the host immune system, through such strategies as migra- tion, surface shedding, antigenic variation, anti-oxidant enzyme production and/or immunomodulation (Behnke et al., 1992; Maizels et al., 2004). In the case of the lat- ter, a range of helminth glycans has been identified as immunomodulators during infection (Harn et al., 2009; Kuijk and van Die, 2010; Van Die and Cummings, 2006; van Die and Cummings, 2010). Previous studies in this laboratory have identified a glycolipid antigen (CarLA) on the surface of infectious- stage larvae (L3) of Trichostrongylid nematodes which infect grazing livestock (Harrison et al., 2003b). While the 0165-2427/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.vetimm.2012.06.024