title: Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway.
abstract: Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs). Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the causative agent of scrub typhus that survives in the cytosol of target cells, induced moDC maturation, as assessed by decreased endocytosis activity, the ability to induce lymphocyte proliferation and the membrane expression of phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and Brucella abortus, the agent of brucellosis, both of which reside in vacuolar compartments, only partly induced the maturation of moDCs, as demonstrated by a phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus to alter moDC activation, we performed microarray and found that C. burnetii and B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and interferon response genes. These genes were down-modulated in response to C. burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide and O. tsutsugamushi. This transcriptional alteration was associated with the defective interferon-β production. This study demonstrates that intracellular bacteria specifically affect moDC responses and emphasizes how C. burnetii and B. abortus interfere with moDC activation and the antimicrobial immune response. We believe that comparing infection by several bacterial species may be useful for defining new pathways and biomarkers and for developing new treatment strategies.
authors.affiliation: Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gorvel
authors.affiliation: Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Textoris
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, United States of America.
authors.forename: Romain
authors.initials: R
authors.lastname: Banchereau
authors.affiliation: Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, Marseille, France.
authors.forename: Amira
authors.initials: A
authors.lastname: Ben Amara
authors.affiliation: Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, Marseille, France; Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Wiwit
authors.initials: W
authors.lastname: Tantibhedhyangkul
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, INSERM, U1104, CNRS, UMR7280, Marseille, France.
authors.forename: Kristin
authors.initials: K
authors.lastname: von Bargen
authors.affiliation: Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, Marseille, France.
authors.forename: Mignane B
authors.initials: MB
authors.lastname: Ka
authors.affiliation: Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Capo
authors.affiliation: Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Ghigo
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, INSERM, U1104, CNRS, UMR7280, Marseille, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
authors.affiliation: Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, Marseille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
mesh_terms: D000818:Animals; D002003:Brucella abortus / Q000502:physiology*; D002454:Cell Differentiation; D016997:Coxiella burnetii / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D042541:Intracellular Space / Q000382:microbiology*; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010766:Phosphorylation; D015398:Signal Transduction; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016899:Interferon-beta; D048051:p38 Mitogen-Activated Protein Kinases