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* Programme of Gastrointestinal Tract Biology and Health, Institute of Food Research, Norwich, United Kingdom;
Technology Research Group, Babraham Institute, Cambridge, United Kingdom;
Department of Pharmacology, University of Siena, Siena, Italy; and
Department of Microbiology, Ohio State University, Columbus, OH 43210
It has been shown previously that certain bacteria rapidly (3 h) up-regulated in vivo microfold cell (M cell)-mediated transport of Ag across the follicle-associated epithelium of intestinal Peyer’s patch. Our aim was to determine whether soluble mediators secreted following host-bacteria interaction were involved in this event. A combination of proteomics and immunohistochemical analyses was used to identify molecules produced in the gut in response to bacterial challenge in vivo; their effects were then tested on human intestinal epithelial cells in vitro. Macrophage migration inhibitory factor (MIF) was the only cytokine produced rapidly after in vivo bacterial challenge by CD11c+ cells located beneath the M cell-rich area of the follicle-associated epithelium of the Peyer’s patch. Subsequently, in vitro experiments conducted using human Caco-2 cells showed that, within hours, MIF induced the appearance of cells that showed temperature-dependent transport of microparticles and M cell-specific bacterium Vibrio cholerae, and acquired biochemical features of M cells. Furthermore, using an established in vitro human M cell model, we showed that anti-MIF Ab blocked Raji B cell-mediated conversion of Caco-2 cells into Ag-sampling cells. Finally, we report that MIF–/– mice, in contrast to wild-type mice, failed to show increased M cell-mediated transport following in vivo bacterial challenge. These data show that MIF plays a role in M cell-mediated transport, and cross-talk between bacteria, gut epithelium, and immune system is instrumental in regulating key functions of the gut, including M cell-mediated Ag sampling.
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1 This work was supported by research grants from Department for Environment, Food and Rural Affairs (to M.J.T.), Biotechnology and Biological Sciences Research Council (to C.N.), and National Institutes of Health R01 AI51823 (to A.R.S.). Work at Institute of Food Research and Babraham Institute is supported by the Biotechnology and Biological Sciences Research Council.
2 Current address: Protein Technology Group, Babraham Bioscience Technologies, Cambridge, United Kingdom.
3 Address correspondence and reprint requests to Dr. Claudio Nicoletti, Laboratory of Mucosal Immunology, Programme of Gastrointestinal Biology and Health, Institute of Food Research, Colney, Norwich NR4 7UA, United Kingdom. E-mail address: claudio.nicoletti{at}bbsrc.ac.uk
4 Abbreviations used in this paper: M cell, microfold cell; 2D, two-dimensional; FAE, follicle-associated epithelium; MIF, macrophage migration inhibitory factor; Pn, pneumococci; PP, Peyer’s patch; SI, sucrase isomaltase; TEER, transepithelial electric resistance; TEM, transmission electron microscopy; ZO-1, zonula occludens 1.
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