PMID- 29155090 OWN - NLM STAT- MEDLINE DCOM- 20190807 LR - 20190807 IS - 1876-7737 (Electronic) IS - 1874-3919 (Linking) VI - 180 DP - 2018 May 30 TI - Proteome and phosphoproteome analysis of commensally induced dendritic cell maturation states. PG - 11-24 LID - S1874-3919(17)30380-9 [pii] LID - 10.1016/j.jprot.2017.11.008 [doi] AB - Dendritic cells (DCs) can shape the immune system towards an inflammatory or tolerant state depending on the bacterial antigens and the environment they encounter. In this study we provide a proteomic catalogue of differentially expressed proteins between distinct DC maturation states, brought about by bacteria that differ in their endotoxicity. To achieve this, we have performed proteomics and phosphoproteomics on murine DC cultures. Symbiont and pathobiont bacteria were used to direct dendritic cells into a semi-mature and fully-mature state, respectively. The comparison of semi-mature and fully-mature DCs revealed differential expression in 103 proteins and differential phosphorylation in 118 phosphosites, including major regulatory factors of central immune processes. Our analyses predict that these differences are mediated by upstream elements such as SOCS1, IRF3, ABCA1, TLR4, and PTGER4. Our analyses indicate that the symbiont bacterial strain affects DC proteome in a distinct way, by downregulating inflammatory proteins and activating anti-inflammatory upstream regulators. Biological significance In this study we have investigated the responses of immune cells to distinct bacterial stimuli. We have used the symbiont bacterial strain B. vulgatus and the pathobiont E. coli strain to stimulate cultured primary dendritic cells and performed a shotgun proteome analysis to investigate the protein expression and phosphorylation level differences on a genome level. We have observed expression and phosphorylation level differences in key immune regulators, transcription factors and signal transducers. Moreover, our subsequent bioinformatics analysis indicated regulation at several signaling pathways such as PPAR signaling, LXR/RXR activation and glucocorticoid signaling pathways, which are not studied in detail in an inflammation and DC maturation context. Our phosphoproteome analysis showed differential phosphorylation in 118 phosphosites including those belonging to epigenetic regulators, transcription factors and major cell cycle regulators. We anticipate that our study will facilitate further investigation of immune cell proteomes under different inflammatory and non-inflammatory conditions. CI - Copyright (c) 2017. Published by Elsevier B.V. FAU - Korkmaz, Ali Giray AU - Korkmaz AG AD - Institute of Medical Microbiology and Hygiene, University of Tubingen, Germany. Electronic address: giray.korkmaz@med.uni-tuebingen.de. FAU - Popov, Todor AU - Popov T AD - Institute of Medical Microbiology and Hygiene, University of Tubingen, Germany. FAU - Peisl, Loulou AU - Peisl L AD - Institute of Medical Microbiology and Hygiene, University of Tubingen, Germany. FAU - Codrea, Marius Cosmin AU - Codrea MC AD - Quantitative Biology Center, University of Tubingen, Germany. FAU - Nahnsen, Sven AU - Nahnsen S AD - Quantitative Biology Center, University of Tubingen, Germany. FAU - Steimle, Alexander AU - Steimle A AD - Institute of Medical Microbiology and Hygiene, University of Tubingen, Germany. FAU - Velic, Ana AU - Velic A AD - Proteome Center, University of Tubingen, Germany. FAU - Macek, Boris AU - Macek B AD - Proteome Center, University of Tubingen, Germany. FAU - von Bergen, Martin AU - von Bergen M AD - Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany. FAU - Bernhardt, Joerg AU - Bernhardt J AD - Ernst-Moritz-Arndt Universitat Greifswald, Institute for Microbiology, Germany. FAU - Frick, Julia-Stefanie AU - Frick JS AD - Institute of Medical Microbiology and Hygiene, University of Tubingen, Germany. LA - eng PT - Journal Article DEP - 20171115 PL - Netherlands TA - J Proteomics JT - Journal of proteomics JID - 101475056 RN - 0 (Phosphoproteins) RN - 0 (Proteome) MH - Animals MH - *Bacteroides MH - Bacteroides Infections/*metabolism MH - Dendritic Cells/*metabolism/pathology MH - *Escherichia coli MH - Escherichia coli Infections/*metabolism MH - Female MH - Mice MH - Phosphoproteins/*biosynthesis MH - Proteome/*biosynthesis MH - Proteomics OTO - NOTNLM OT - B. vulgatus OT - Commensals OT - Dendritic cells OT - Expression analysis OT - Inflammation OT - Shotgun proteomics EDAT- 2017/11/21 06:00 MHDA- 2019/08/08 06:00 CRDT- 2017/11/21 06:00 PHST- 2017/02/17 00:00 [received] PHST- 2017/09/18 00:00 [revised] PHST- 2017/11/14 00:00 [accepted] PHST- 2017/11/21 06:00 [pubmed] PHST- 2019/08/08 06:00 [medline] PHST- 2017/11/21 06:00 [entrez] AID - S1874-3919(17)30380-9 [pii] AID - 10.1016/j.jprot.2017.11.008 [doi] PST - ppublish SO - J Proteomics. 2018 May 30;180:11-24. doi: 10.1016/j.jprot.2017.11.008. Epub 2017 Nov 15.