title: Macrophage migration inhibitory factor plays a role in the regulation of microfold (M) cell-mediated transport in the gut.
abstract: 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.
authors.affiliation: Programme of Gastrointestinal Tract Biology and Health, Institute of Food Research, Norwich, United Kingdom.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Man
authors.forename: Federica
authors.initials: F
authors.lastname: Lodi
authors.forename: Eugenio
authors.initials: E
authors.lastname: Bertelli
authors.forename: Mari
authors.initials: M
authors.lastname: Regoli
authors.forename: Carmen
authors.initials: C
authors.lastname: Pin
authors.forename: Francis
authors.initials: F
authors.lastname: Mulholland
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taussig
authors.forename: Claudio
authors.initials: C
authors.lastname: Nicoletti
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001419:Bacteria / Q000276:immunology*; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology*; D001692:Biological Transport / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D018938:Caco-2 Cells; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007410:Intestinal Diseases / Q000276:immunology* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D007421:Intestine, Small / Q000276:immunology* / Q000382:microbiology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology* / Q000382:microbiology; D011817:Rabbits
chemical_list: D000942:Antigens, Bacterial; D039521:CD11c Antigen; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C076231:Mif protein, mouse