title: Brucella discriminates between mouse dendritic cell subsets upon in vitro infection.
abstract: Brucella is a Gram-negative bacterium responsible for brucellosis, a worldwide re-emerging zoonosis. Brucella has been shown to infect and replicate within Granulocyte macrophage colony-stimulating factor (GMCSF) in vitro grown bone marrow-derived dendritic cells (BMDC). In this cell model, Brucella can efficiently control BMDC maturation. However, it has been shown that Brucella infection in vivo induces spleen dendritic cells (DC) migration and maturation. As DCs form a complex network composed by several subpopulations, differences observed may be due to different interactions between Brucella and DC subsets. Here, we compare Brucella interaction with several in vitro BMDC models. The present study shows that Brucella is capable of replicating in all the BMDC models tested with a high infection rate at early time points in GMCSF-IL15 DCs and Flt3l DCs. GMCSF-IL15 DCs and Flt3l DCs are more activated than the other studied DC models and consequently intracellular bacteria are not efficiently targeted to the ER replicative niche. Interestingly, GMCSF-DC and GMCSF-Flt3l DC response to infection is comparable. However, the key difference between these 2 models concerns IL10 secretion by GMCSF DCs observed at 48 h post-infection. IL10 secretion can explain the weak secretion of IL12p70 and TNFα in the GMCSF-DC model and the low level of maturation observed when compared to GMCSF-IL15 DCs and Flt3l DCs. These models provide good tools to understand how Brucella induce DC maturation in vivo and may lead to new therapeutic design using DCs as cellular vaccines capable of enhancing immune response against pathogens.
authors.affiliation: a Centre d'Immunologie de Marseille-Luminy; Aix Marseille Université; CNRS UMR7280; INSERM U1104 ; Marseille , France.
authors.forename: Alexia
authors.initials: A
authors.lastname: Papadopoulos
authors.affiliation: a Centre d'Immunologie de Marseille-Luminy; Aix Marseille Université; CNRS UMR7280; INSERM U1104 ; Marseille , France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gagnaire
authors.affiliation: a Centre d'Immunologie de Marseille-Luminy; Aix Marseille Université; CNRS UMR7280; INSERM U1104 ; Marseille , France.
authors.forename: Clara
authors.initials: C
authors.lastname: Degos
authors.affiliation: a Centre d'Immunologie de Marseille-Luminy; Aix Marseille Université; CNRS UMR7280; INSERM U1104 ; Marseille , France.
authors.forename: Chantal
authors.initials: C
authors.lastname: de Chastellier
authors.affiliation: a Centre d'Immunologie de Marseille-Luminy; Aix Marseille Université; CNRS UMR7280; INSERM U1104 ; Marseille , France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
mesh_terms: D000818:Animals; D002002:Brucella / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D054884:Host-Pathogen Interactions; D016753:Interleukin-10 / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Brucella; cell activation; dendritic cell; in vitro models; infectious disease