Human Dendritic Cells with Th2-Polarizing Capacity: Analysis Using Label-Free Quantitative Proteomics

Abstract

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-γ 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.

Schistosome immunomodulators

“…Thus, the observed inhibition in protein synthesis in ω1-treated DCs is a combined effect of degradation of mRNA transcripts and interference with ribosomal integrity caused by rRNA cleavage. However, analysis of DCs 32 hours after exposure to ω1 (or SEA) reveals that RNA degradation is not uniform; there is substantially increased expression of certain genes, e.g., ribosomal protein P2 and synaptic vesicle amine transferase-1 [ 165 ]. Cumulatively, these changes are said to lead to reduced DC–T cell interaction, a setting that favors Th2 polarization [ 160 ].…”

Secretome Analysis of Mouse Dendritic Cells Interacting with a Probiotic Strain of Lactobacillus gasseri

“…Proteomics have been widely applied to elucidate differences in whole-cell protein patterns of immature DCs (iDCs) and mature DCs (mDCs), and to study exosome proteome, and, recently, phagosomal proteome [8][9][10][11][12][13]. However, only a few proteomic studies have characterized the protein pattern secreted (secretome) by iDCs and mDCs [14][15][16].…”

Fasciola gigantica excretory-secretory products (FgESPs) modulate the differentiation and immune functions of buffalo dendritic cells through a mechanism involving DNMT1 and TET1

“…Among the immune cells, DCs as the major well-known antigen-presenting cells (APCs) linking innate and adaptive immunity, play a key role in the initiation of protective pro-inflammatory as well as tolerogenic immune responses through continuously capturing and responding to the pathogenic antigens from microenvironment [ 13 ]. Helminths and helminth-derived molecules condition DCs to generate a non-classical maturation during infection, and prime a protective Th2 or Treg response which cause less damage to either the parasite or the host [ 14 , 15 ]. These multicellular flukes, unlike protozoans and microorganisms, release excretory-secretory products (ESPs) to influence the host immune system as a useful strategy for survival.…”