PMID- 29046388 OWN - NLM STAT- MEDLINE DCOM- 20190103 LR - 20210217 IS - 1535-9484 (Electronic) IS - 1535-9476 (Print) IS - 1535-9476 (Linking) VI - 17 IP - 1 DP - 2018 Jan TI - The Early Dendritic Cell Signaling Induced by Virulent Francisella tularensis Strain Occurs in Phases and Involves the Activation of Extracellular Signal-Regulated Kinases (ERKs) and p38 In the Later Stage. PG - 81-94 LID - 10.1074/mcp.RA117.000160 [doi] AB - Dendritic cells (DCs) infected by Francisella tularensis are poorly activated and do not undergo classical maturation process. Although reasons of such unresponsiveness are not fully understood, their impact on the priming of immunity is well appreciated. Previous attempts to explain the behavior of Francisella-infected DCs were hypothesis-driven and focused on events at later stages of infection. Here, we took an alternative unbiased approach by applying methods of global phosphoproteomics to analyze the dynamics of cell signaling in primary DCs during the first hour of infection by Francisella tularensis Presented results show that the early response of DCs to Francisella occurs in phases and that ERK and p38 signaling modules induced at the later stage are differentially regulated by virulent and attenuated DeltadsbA strain. These findings imply that the temporal orchestration of host proinflammatory pathways represents the integral part of Francisella life-cycle inside hijacked DCs. CI - (c) 2018 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Fabrik, Ivo AU - Fabrik I AD - From the double daggerDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic. FAU - Link, Marek AU - Link M AD - From the double daggerDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic. FAU - Putzova, Daniela AU - Putzova D AD - From the double daggerDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic. FAU - Plzakova, Lenka AU - Plzakova L AD - From the double daggerDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic. FAU - Lubovska, Zuzana AU - Lubovska Z AD - section signInstitute of Molecular Genetics ASCR v.v.i., Microscopy Centre, Electron Microscopy Core Facility, 142 20 Prague 4, Czech Republic. FAU - Philimonenko, Vlada AU - Philimonenko V AD - section signInstitute of Molecular Genetics ASCR v.v.i., Microscopy Centre, Electron Microscopy Core Facility, 142 20 Prague 4, Czech Republic. AD - paragraph signInstitute of Molecular Genetics ASCR v.v.i., Department of Biology of the Cell Nucleus, 142 20 Prague 4, Czech Republic. FAU - Pavkova, Ivona AU - Pavkova I AD - From the double daggerDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic. FAU - Rehulka, Pavel AU - Rehulka P AD - From the double daggerDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic. FAU - Krocova, Zuzana AU - Krocova Z AD - From the double daggerDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic. FAU - Hozak, Pavel AU - Hozak P AD - section signInstitute of Molecular Genetics ASCR v.v.i., Microscopy Centre, Electron Microscopy Core Facility, 142 20 Prague 4, Czech Republic. AD - paragraph signInstitute of Molecular Genetics ASCR v.v.i., Department of Biology of the Cell Nucleus, 142 20 Prague 4, Czech Republic. FAU - Santic, Marina AU - Santic M AD - ||Department of Microbiology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. FAU - Stulik, Jiri AU - Stulik J AD - From the double daggerDepartment of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, 500 01 Hradec Kralove, Czech Republic; jiri.stulik@unob.cz. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171018 PL - United States TA - Mol Cell Proteomics JT - Molecular & cellular proteomics : MCP JID - 101125647 RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cell Line MH - Dendritic Cells/*metabolism/microbiology MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Female MH - *Francisella tularensis MH - Mice, Inbred C57BL MH - Phosphorylation MH - Tularemia/*metabolism MH - p38 Mitogen-Activated Protein Kinases/*metabolism PMC - PMC5750852 EDAT- 2017/10/20 06:00 MHDA- 2019/01/04 06:00 PMCR- 2019/01/01 CRDT- 2017/10/20 06:00 PHST- 2017/06/27 00:00 [received] PHST- 2017/09/22 00:00 [revised] PHST- 2017/10/20 06:00 [pubmed] PHST- 2019/01/04 06:00 [medline] PHST- 2017/10/20 06:00 [entrez] PHST- 2019/01/01 00:00 [pmc-release] AID - S1535-9476(20)32285-4 [pii] AID - RA117.000160 [pii] AID - 10.1074/mcp.RA117.000160 [doi] PST - ppublish SO - Mol Cell Proteomics. 2018 Jan;17(1):81-94. doi: 10.1074/mcp.RA117.000160. Epub 2017 Oct 18.