title: Natural killer cells protect against mucosal and systemic infection with the enteric pathogen Citrobacter rodentium.
abstract: Natural killer (NK) cells are traditionally considered in the context of tumor surveillance and viral defense, but their role in bacterial infections, particularly those caused by enteric pathogens, is less clear. C57BL/6 mice were orally gavaged with Citrobacter rodentium, a murine pathogen related to human diarrheagenic Escherichia coli. We used polyclonal anti-asialo GM1 antibody to actively deplete NK cells in vivo. Bioluminescent imaging and direct counts were used to follow infection. Flow cytometry and immunofluorescence microscopy were used to analyze immune responses. During C. rodentium infection, NK cells were recruited to mucosal tissues, where they expressed a diversity of immune-modulatory factors. Depletion of NK cells led to higher bacterial loads but less severe colonic inflammation, associated with reduced immune cell recruitment and lower cytokine levels. NK cell-depleted mice also developed disseminated systemic infection, unlike control infected mice. NK cells were also cytotoxic to C. rodentium in vitro.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland. Lindsay.Hall@uea.ac.uk
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Hall
authors.forename: Carola T
authors.initials: CT
authors.lastname: Murphy
authors.forename: Grainne
authors.initials: G
authors.lastname: Hurley
authors.forename: Aoife
authors.initials: A
authors.lastname: Quinlan
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Nally
authors.forename: Silvia
authors.initials: S
authors.lastname: Melgar
mesh_terms: D000818:Animals; D002432:Cecum / Q000276:immunology; D044082:Citrobacter rodentium / Q000276:immunology* / Q000472:pathogenicity; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology; D005260:Female; D007155:Immunologic Factors / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors