PMID- 29130972 OWN - NLM STAT- MEDLINE DCOM- 20171229 LR - 20171229 IS - 1423-0097 (Electronic) IS - 1018-2438 (Linking) VI - 174 IP - 3-4 DP - 2017 TI - Human Dendritic Cells with Th2-Polarizing Capacity: Analysis Using Label-Free Quantitative Proteomics. PG - 170-182 LID - 10.1159/000479512 [doi] AB - BACKGROUND: Dendritic cells (DCs) are the sentinels of the immune system. Upon recognition of a pathogen, they mature and migrate to draining lymph nodes to prime and polarize T cell responses. Although it is known that helminths and helminth-derived molecules condition DCs to polarize T helper (Th) cells towards Th2, the underlying mechanisms remain incompletely understood. OBJECTIVES: The aim of this study was to conduct a proteome analysis of helminth antigen-stimulated DCs in order to gain more insight into the cellular processes associated with their ability to polarize immune responses. METHODS: We analyzed the maturation and polarization of monocyte-derived DCs from 9 donors at 2 different time points after stimulation with different Th1- and Th2-polarizing pathogen-derived molecules. The samples were measured using liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry for relative quantitation. RESULTS: Lipopolysaccharide-induced maturation promoted the expression of proteins related to metabolic, cellular, and immune system processes. Th1-polarizing DCs, conditioned by IFN-gamma during maturation, displayed accelerated maturation by differentially expressing cytoskeletal proteins and proteins involved in immune regulation. The stimulation of DCs with soluble egg antigens and omega-1 derived from Schistosoma mansoni, which are both Th2-inducing stimuli, increased 60S acidic ribosomal protein P2, and vesicle amine transferase 1 while decreasing the expression of proteins related to antigen processing and presentation. CONCLUSION: Our data indicate that not only proteins involved in the interaction between T cells and DCs at the level of the immunological synapse, but also those related to cellular metabolism and stress, may promote Th2 polarization. CI - (c) 2017 S. Karger AG, Basel. FAU - Hussaarts, Leonie AU - Hussaarts L AD - Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands. FAU - Kaisar, Maria Mardalena Martini AU - Kaisar MMM FAU - Guler, Arzu Tugce AU - Guler AT FAU - Dalebout, Hans AU - Dalebout H FAU - Everts, Bart AU - Everts B FAU - Deelder, Andre M AU - Deelder AM FAU - Palmblad, Magnus AU - Palmblad M FAU - Yazdanbakhsh, Maria AU - Yazdanbakhsh M LA - eng PT - Journal Article DEP - 20171110 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (Antigens, Helminth) RN - 0 (Egg Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (omega-1 antigen, Schistosoma mansoni) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antigen Presentation MH - Antigens, Helminth/immunology MH - Cell Differentiation MH - Cells, Cultured MH - Dendritic Cells/*immunology MH - Egg Proteins/immunology MH - Humans MH - Immune Evasion MH - Interferon-gamma/immunology MH - Lipopolysaccharides/immunology MH - Proteomics MH - Schistosoma mansoni/*immunology MH - Schistosomiasis mansoni/*immunology MH - Th1 Cells/*immunology MH - Th2 Cells/*immunology OTO - NOTNLM OT - Dendritic cells OT - Helminths OT - Omega-1 OT - Proteome OT - T helper 2 responses EDAT- 2017/11/14 06:00 MHDA- 2017/12/30 06:00 CRDT- 2017/11/14 06:00 PHST- 2017/01/19 00:00 [received] PHST- 2017/07/11 00:00 [accepted] PHST- 2017/11/14 06:00 [pubmed] PHST- 2017/12/30 06:00 [medline] PHST- 2017/11/14 06:00 [entrez] AID - 000479512 [pii] AID - 10.1159/000479512 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2017;174(3-4):170-182. doi: 10.1159/000479512. Epub 2017 Nov 10.