title: Qualitatively distinct patterns of cytokines are released by human dendritic cells in response to different pathogens.
abstract: Dendritic cells produce cytokines that regulate the class of the adaptive immune response. Microbial recognition is mediated, at least in part, by pattern recognition receptors such as Toll-like receptors, which influence dendritic cell maturation. In humans it is not yet clear how intact pathogens modulate the developing immune response. To address the effects of intact pathogens on the maturation and effector functions of human dendritic cells, we investigated their responses to a number of microbial pathogens. We studied a range of micro-organisms including Gram-negative bacteria (Escherichia coli and Salmonella enterica sv. typhimurium), Gram-positive cocci (Staphylococcus aureus) and atypical bacteria (Mycobacterium tuberculosis and Mycoplasma hominis) as well as the human protozoal parasite Trichomonas vaginalis. The micro-organisms were fixed in formaldehyde to prevent replication whilst preserving surface morphology. All the pathogens induced similar up-regulation of dendritic cell activation-associated cell surface markers but there was a profound difference in the patterns of cytokines produced by the stimulated dendritic cells. Some pathogens (E. coli, Salmonella enterica sv. typhimurium and S. aureus) induced interleukin-12 (IL-12), IL-10 and interferon-alpha whereas others (M. tuberculosis, Mycoplasma hominis and T. vaginalis) induced only IL-10. This differential effect was not altered by costimulation of the dendritic cells through CD40. These results support the notion that human dendritic cells are plastic in their response to microbial stimuli and that the nature of the pathogen dictates the response of the dendritic cell.
authors.affiliation: Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College at Hammersmith Hospital, London, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Scott
authors.forename: Maria
authors.initials: M
authors.lastname: Manunta
authors.forename: Conrad
authors.initials: C
authors.lastname: Germain
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.forename: Meleri
authors.initials: M
authors.lastname: Jones
authors.forename: Peter
authors.initials: P
authors.lastname: Mitchell
authors.forename: Daniele
authors.initials: D
authors.lastname: Dessi
authors.forename: Kathleen
authors.initials: K
authors.lastname: Branigan Bamford
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Fiori
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008024:Ligands; D014246:Trichomonas vaginalis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D000953:Antigens, Protozoan; D019013:CD40 Antigens; D016207:Cytokines; D007370:Interferon Type I; D008024:Ligands; D016753:Interleukin-10; D018664:Interleukin-12