title: CX3CR1+ Cell-Mediated Salmonella Exclusion Protects the Intestinal Mucosa during the Initial Stage of Infection.
abstract: During Salmonella Typhimurium infection, intestinal CX3CR1+cells can either extend transepithelial cellular processes to sample luminal bacteria or, very early after infection, migrate into the intestinal lumen to capture bacteria. However, until now, the biological relevance of the intraluminal migration of CX3CR1+cells remained to be determined. We addressed this by using a combination of mouse strains differing in their ability to carry out CX3CR1-mediated sampling and intraluminal migration. We observed that the number of S. Typhimurium traversing the epithelium did not differ between sampling-competent/migration-competent C57BL/6 and sampling-deficient/migration-competent BALB/c mice. In contrast, in sampling-deficient/migration-deficient CX3CR1-/-mice the numbers of S. Typhimurium penetrating the epithelium were significantly higher. However, in these mice the number of invading S. Typhimurium was significantly reduced after the adoptive transfer of CX3CR1+cells directly into the intestinal lumen, consistent with intraluminal CX3CR1+cells preventing S. Typhimurium from infecting the host. This interpretation was also supported by a higher bacterial fecal load in CX3CR1+/gfpcompared with CX3CR1gfp/gfpmice following oral infection. Furthermore, by using real-time in vivo imaging we observed that CX3CR1+cells migrated into the lumen moving through paracellular channels within the epithelium. Also, we reported that the absence of CX3CR1-mediated sampling did not affect Ab responses to a noninvasive S. Typhimurium strain that specifically targeted the CX3CR1-mediated entry route. These data showed that the rapidly deployed CX3CR1+cell-based mechanism of immune exclusion is a defense mechanism against pathogens that complements the mucous and secretory IgA Ab-mediated system in the protection of intestinal mucosal surface.
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, United Kingdom.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Man
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, United Kingdom.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Gicheva
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
authors.forename: Mari
authors.initials: M
authors.lastname: Regoli
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
authors.forename: Gary
authors.initials: G
authors.lastname: Rowley
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Cunto
authors.affiliation: Analytical Sciences Unit, Institute of Food Research, Norwich NR4 7UA, United Kingdom; and.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Wellner
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bassity
authors.affiliation: Section of Human Anatomy, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gulisano
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
authors.forename: Eugenio
authors.identifier: 0000-0002-9681-4556
authors.initials: E
authors.lastname: Bertelli
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, United Kingdom; claudio.nicoletti@unifi.it claudio.nicoletti@ifr.ac.uk.|Section of Human Anatomy, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Claudio
authors.identifier: 0000-0002-6242-4867
authors.initials: C
authors.lastname: Nicoletti
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine