PMID- 24915541 OWN - NLM STAT- MEDLINE DCOM- 20150129 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 6 DP - 2014 TI - Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway. PG - e99420 LID - 10.1371/journal.pone.0099420 [doi] LID - e99420 AB - 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-beta 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. FAU - Gorvel, Laurent AU - Gorvel L AD - Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Universite, Marseille, France. FAU - Textoris, Julien AU - Textoris J AD - Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Universite, Marseille, France. FAU - Banchereau, Romain AU - Banchereau R AD - Baylor Institute for Immunology Research, Dallas, Texas, United States of America. FAU - Ben Amara, Amira AU - Ben Amara A AD - Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Universite, Marseille, France. FAU - Tantibhedhyangkul, Wiwit AU - Tantibhedhyangkul W AD - Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Universite, Marseille, France; Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. FAU - von Bargen, Kristin AU - von Bargen K AD - Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, INSERM, U1104, CNRS, UMR7280, Marseille, France. FAU - Ka, Mignane B AU - Ka MB AD - Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Universite, Marseille, France. FAU - Capo, Christian AU - Capo C AD - Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Universite, Marseille, France. FAU - Ghigo, Eric AU - Ghigo E AD - Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Universite, Marseille, France. FAU - Gorvel, Jean-Pierre AU - Gorvel JP AD - Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, INSERM, U1104, CNRS, UMR7280, Marseille, France. FAU - Mege, Jean-Louis AU - Mege JL AD - Centre National de la Recherche Scientifique UMR 7278, IRD198, INSERM U1095, Aix-Marseille Universite, Marseille, France. LA - eng PT - Journal Article DEP - 20140610 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 77238-31-4 (Interferon-beta) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Brucella abortus/*physiology MH - Cell Differentiation MH - Coxiella burnetii/*physiology MH - Dendritic Cells/*immunology MH - Gene Expression Profiling MH - Humans MH - Interferon-beta/metabolism MH - Intracellular Space/*microbiology MH - Mice, Inbred BALB C MH - Monocytes/cytology MH - Oligonucleotide Array Sequence Analysis MH - Phenotype MH - Phosphorylation MH - *Signal Transduction MH - Transcription, Genetic MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC4051653 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/06/11 06:00 MHDA- 2015/01/30 06:00 PMCR- 2014/06/10 CRDT- 2014/06/11 06:00 PHST- 2014/01/28 00:00 [received] PHST- 2014/05/14 00:00 [accepted] PHST- 2014/06/11 06:00 [entrez] PHST- 2014/06/11 06:00 [pubmed] PHST- 2015/01/30 06:00 [medline] PHST- 2014/06/10 00:00 [pmc-release] AID - PONE-D-14-03256 [pii] AID - 10.1371/journal.pone.0099420 [doi] PST - epublish SO - PLoS One. 2014 Jun 10;9(6):e99420. doi: 10.1371/journal.pone.0099420. eCollection 2014.