Parasite Immunology, 2009, 31, 123–131 DOI: 10.1111/j.1365-3024.2008.01088.x SBOIlRiascoIkGlnawItNelaAnPLtuigbAelniRshTsiIntCigmLuvEltadteAPCiderivtedILr-10anodIL-6 antigen presenting cell-derived IL-10 and IL-6 correlate with Trichuris muris isolate-speciﬁc survival R. D’ELIA & K. J. ELSE Faculty of Life Sciences, University of Manchester, Manchester, UK SUMMARY Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist — the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate-speciﬁc E/S with bone marrow-derived macrophages (BMMΦ) and dendritic cells (BMDCs) in vitro. Markers of co-stimulation and levels of MHC-II were analysed by FACS and cytokine levels in supernatants quantiﬁed. E/S antigens from the S iso- late consistently stimulated signiﬁcantly higher levels of IL-10 and IL-6 from both macrophages (F4/80+CD11b+CD11c–) and dendritic cells (CD11c+CD11b+F4/80–) compared to J and E isolate E/S. If these in vitro differences in APC-derived cytokines, particularly IL-10, are biologically signiﬁcant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective. Keywords macrophages, dendritic cells, Trichuris muris, IL-6 and IL-10 Correspondence: Riccardo D’Elia, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK (e-mail: riccardo.d’elia@postgrad.manchester.ac.uk). Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/online open#OnlineOpen_Terms Received: 29 August 2008 Accepted for publication: 31 October 2008 Abbreviations: APCs, antigen presenting cells; BMMΦ, bone marrow derived macrophages; BMDCs, bone marrow derived dendritic cells; E/S, excretory/secretory antigen © 2009 The Authors Journal compilation © 2009 Blackwell Publishing Ltd INTRODUCTION Trichuris muris is a natural helminth of mice and serves as a relevant model for the infection of humans with the gastrointestinal nematode parasite T. trichiura (1). Trichuris trichiura is believed to infect around 1 billion people worldwide. Through the use of this laboratory model, our understanding of immunity to intestinal parasites has signiﬁcantly increased. Thus it is now well-established that resistance to T. muris is associated with a dominant T helper (Th) 2 response and susceptibility a Th1 response (2,3). The majority of T. muris studies focus on one particular isolate, the Edinburgh (E) isolate, however, two other isolates exist, the Japan (J) and Sobreda (S) isolates. Remarkably, the S isolate of T. muris is able to survive to chronicity in the C57BL/6 mouse; whereas the other two isolates are readily expelled from the same strain of mouse (4 –7). Little is known about the underlying mechanisms associated with S isolate survival. Previous published data from our laboratory suggested that the differences in expulsion kinetics in vivo could be associated with a difference in protein make-up of the excretory/ secretory products (E/S) between the isolates (7). E/S products from helminths are antigenic but are also believed to have immunomodulatory properties, and this may explain why helminths protect against the development of autoimmunity and allergy (8–10). E/S products from Ascaris suum and Nippostrongylus brasiliensis have both been shown to inhibit lung inﬂammation by suppressing levels of IL-4 and IL-5 (11,12). E/S products are a very heterogeneous mix; research therefore, has started to focus on speciﬁc proteins within the E/S. Of particular interest is the immunomodulatory properties of a 62 kDa protein isolated from Acanthocheilonema viteae (13). ES-62 is the major secreted glycoprotein of the rodent ﬁlarial nematode A. viteae and contains the unusual post-translational modiﬁcation of phosphorylcholine (PC) addition (14 –16). ES-62 has been shown to have a wide range of immunomod- ulatory properties and has been shown to be effective as a 123