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* Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester, United Kingdom;
Bioimaging Facility, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom;
Antigen Presentation Research Group, Division of Investigative Sciences, Faculty of Medicine, Imperial College London, Harrow, United Kingdom;
Klinikum der Universität Regensburg, Regensburg, Germany; and
¶ Institute of Food Research and the University of East Anglia, Colney, United Kingdom
The large intestine is a major site of infection and disease, yet little is known about how immunity is initiated within this site and the role of dendritic cells (DCs) in this process. We used the well-established model of Trichuris muris infection to investigate the innate response of colonic DCs in mice that are inherently resistant or susceptible to infection. One day postinfection, there was a significant increase in the number of immature colonic DCs in resistant but not susceptible mice. This increase was sustained at day 7 postinfection in resistant mice when the majority of the DCs were mature. There was no increase in DC numbers in susceptible mice until day 13 postinfection. In resistant mice, most colonic DCs were located in or adjacent to the epithelium postinfection. There were also marked differences in the expression of colonic epithelial chemokines in resistant mice and susceptible mice. Resistant mice had significantly increased levels of epithelium-derived CCL2, CCL3, CCL5, and CCL20 compared with susceptible mice. Furthermore, administering neutralizing CCL5 and CCL20 Abs to resistant mice prevented DC recruitment. This study provides clear evidence of differences in the kinetics of DC responses in hosts inherently resistant and susceptible to infection. DC responses in the colon correlate with resistance to infection. Differences in the production of DC chemotactic chemokines by colonic epithelial cells in response to infection in resistant vs susceptible mice may explain the different kinetics of the DC response.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Wellcome Trust grants (to S.R.C., S.M.C., and K.J.E.), and Action Medical Research Grant (to S.R.C. and S.M.C.) and a grant funded from The Royal Society (to S.M.C.).
2 Address correspondence and reprint requests to Dr. Sheena M. Cruickshank, Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester M14 9PT, United Kingdom. E-mail address: Sheena.Cruickshank{at}manchester.ac.uk
3 These authors share senior authorship.
4 Abbreviations used in this paper: CEC, colonic epithelial cell; DC, dendritic cell; MHC II, MHC class II; DAPI, 4',6-diamidino-2-phenylindole; MLN, mesenteric lymph node; ES Ag, excretory secretory Ag; TSLP, thymic stromal lymphopoietin.
5 S. M. Cruickshank and S. R. Carding. Submitted for publication.
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