title: Central role for B lymphocytes and CD4+ T cells in immunity to infection by the attaching and effacing pathogen Citrobacter rodentium.
abstract: Citrobacter rodentium, an attaching-effacing bacterial pathogen, establishes an acute infection of the murine colonic epithelium and induces a mild colitis in immunocompetent mice. This study describes the role of T-cell subsets and B lymphocytes in immunity to C. rodentium. C57Bl/6 mice orally infected with C. rodentium resolved infection within 3 to 4 weeks. Conversely, systemic and colonic tissues of RAG1(-/-) mice orally infected with C. rodentium contained high and sustained pathogen loads, and in the colon this resulted in a severe colitis. C57Bl/6 mice depleted of CD4(+) T cells, but not CD8(+) T cells, were highly susceptible to infection and also developed severe colitis. Mice depleted of CD4(+) T cells also had diminished immunoglobulin G (IgG) and IgA antibody responses to two C. rodentium virulence-associated determinants, i.e., EspA and intimin, despite having a massively increased pathogen burden. Mice with an intact T-cell compartment, but lacking B cells ( micro MT mice), were highly susceptible to C. rodentium infection. Systemic immunity, but not mucosal immunity, could be restored by adoptive transfer of convalescent immune sera to infected micro MT mice. Adoptive transfer of immune B cells, but not naïve B cells, provided highly variable immunity to recipient micro MT mice. The results suggest that B-cell-mediated immune responses are central to resolution of a C. rodentium infection but that the mechanism through which this occurs requires further investigation. These data are relevant to understanding immunity to enteric attaching and effacing bacterial pathogens of humans.
authors.affiliation: Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College of Science, Technology and Medicine, South Kensington, London SW6 1SJ, United Kingdom. csimmons@hcm.vnn.vn
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.forename: Marjan
authors.initials: M
authors.lastname: Ghaem-Maghami
authors.forename: Tania K
authors.initials: TK
authors.lastname: Uren
authors.forename: Joanna
authors.initials: J
authors.lastname: Rankin
authors.forename: Allan
authors.initials: A
authors.lastname: Huett
authors.forename: Rob
authors.initials: R
authors.lastname: Goldin
authors.forename: David J
authors.initials: DJ
authors.lastname: Lewis
authors.forename: Thomas T
authors.initials: TT
authors.lastname: MacDonald
authors.forename: Richard A
authors.initials: RA
authors.lastname: Strugnell
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial; D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016971:Citrobacter freundii / Q000276:immunology* / Q000472:pathogenicity*; D003106:Colon / Q000276:immunology / Q000473:pathology; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D016654:Genes, RAG-1; D007121:Immunocompetence; D016867:Immunocompromised Host; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014774:Virulence
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins