NFκB- and MAP-Kinase Signaling Contribute to the Activation of Murine Myeloid Dendritic Cells by a Flagellin A: Allergen Fusion Protein

Moeller, Tobias; Wolfheimer, Sonja; Goretzki, Alexandra; Scheurer, Stephan; Schülke, Stefan

doi:10.3390/cells8040355

Cited by 18 publications

(18 citation statements)

References 69 publications

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“…The MAP kinase activation leads to protein phosphorylation processes, which result in leukotriene and prostaglandin arising. The MAP kinase modifies the transcription factors as well ( Steelman et al, 2015 ; Draber et al, 2016 ; Moeller et al, 2019 ).…”

Section: Sensitization Hypersensitivity/allergic Reactionsmentioning

confidence: 99%

Impact of Probiotic Bacteria on Respiratory Allergy Disorders

Jakubczyk

Górska

2021

Front. Microbiol.

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Respiratory allergy is a common disease with an increased prevalence worldwide. The effective remedy is still unknown, and a new therapeutic approach is highly desirable. The review elaborates the influence of probiotic bacteria on respiratory allergy prevention and treatment with particular emphasis on the impact of the current methods of their administration – oral and intranasal. The background of the respiratory allergy is complex thus, we focused on the usefulness of probiotics in the alleviation of different allergy factors, in particular involved in pathomechanism, local hypersensitive evidence and the importance of epithelial barrier. In this review, we have shown that (1) probiotic strains may vary in modulatory potential in respiratory allergy, (2) probiotic bacteria are beneficial in oral and intranasal administration, (3) recombinant probiotic bacteria can modulate the course of respiratory allergy.

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Section: Sensitization Hypersensitivity/allergic Reactionsmentioning

confidence: 99%

Impact of Probiotic Bacteria on Respiratory Allergy Disorders

Jakubczyk

Górska

2021

Front. Microbiol.

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“…The decreased expression of multiple surface markers and secretion of several cytokines suggests that Tmod1 deficiency may affect the activities of upstream signaling pathways. TLR4 is the receptor for LPS and its downstream MyD88-dependent pathway activates NF-κB and MAPK pathways, which in turn are responsible for the expression of costimulatory molecules and inflammatory cytokines ( 44 , 45 ). Therefore, we compared the activities of these two pathways in LPS-treated Tmod1 +/+ and TOT/Tmod1 -/- imDCs using western blotting.…”

Section: Resultsmentioning

confidence: 99%

Tropomodulin1 Expression Increases Upon Maturation in Dendritic Cells and Promotes Their Maturation and Immune Functions

et al. 2021

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Dendritic cells (DCs) are the most potent antigen-presenting cells. Upon maturation, DCs express costimulatory molecules and migrate to the lymph nodes to present antigens to T cells. The actin cytoskeleton plays key roles in multiple aspects of DC functions. However, little is known about the mechanisms and identities of actin-binding proteins that control DC maturation and maturation-associated functional changes. Tropomodulin1 (Tmod1), an actin-capping protein, controls actin depolymerization and nucleation. We found that Tmod1 was expressed in bone marrow-derived immature DCs and was significantly upregulated upon lipopolysaccharide (LPS)-induced DC maturation. By characterizing LPS-induced mature DCs (mDCs) from Tmod1 knockout mice, we found that compared with Tmod1+/+ mDCs, Tmod1-deficient mDCs exhibited lower surface expression of costimulatory molecules and chemokine receptors and reduced secretion of inflammatory cytokines, suggesting that Tmod1 deficiency retarded DC maturation. Tmod1-deficient mDCs also showed impaired random and chemotactic migration, deteriorated T-cell stimulatory ability, and reduced F-actin content and cell stiffness. Furthermore, Tmod1-deficient mDCs secreted high levels of IFN-β and IL-10 and induced immune tolerance in an experimental autoimmune encephalomyelitis (EAE) mouse model. Mechanistically, Tmod1 deficiency affected TLR4 signaling transduction, resulting in the decreased activity of MyD88-dependent NFκB and MAPK pathways but the increased activity of the TRIF/IRF3 pathway. Rescue with exogenous Tmod1 reversed the effect of Tmod1 deficiency on TLR4 signaling. Therefore, Tmod1 is critical in regulating DC maturation and immune functions by regulating TLR4 signaling and the actin cytoskeleton. Tmod1 may be a potential target for modulating DC functions, a strategy that would be beneficial for immunotherapy for several diseases.

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“…Our previous studies showed that MAPK-mediated activation of both NFκB- and mTOR-signaling likely is a key pathway for IL-10 secretion in TLR5-engaged BMDCs with a flagellin:allergen fusion protein [ 20 , 21 ]. However, in the present study, mechanistically, Man2 activated MAPKs (p38, p42/44, SAP/JNK) and NF-κB at certain levels, but only marginally activated p70S6K in BMDCs.…”

Section: Discussionmentioning

confidence: 99%

“…However, in contrast to IL-10 secretion, secretions of IL-6 and TNF-α were detectable after 72 h culture of Man2-treated BMDCs, similar to the observations in LPS-stimulated cells. Several studies have reported TLR-ligands to induce IL-6 and TNF-α production by activating MAPKs and NF-κB in BMDCs [ 16 , 21 , 23 ]. In addition, recent studies described that a shift from oxidative phosphorylation to anaerobic glycolysis in the metabolism of macrophages and DCs is important for pro-inflammatory cytokine production and effector function of the respective cells [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

β-(1→4)-Mannobiose Acts as an Immunostimulatory Molecule in Murine Dendritic Cells by Binding the TLR4/MD-2 Complex

Cheng

Lin

Saburi

et al. 2021

Cells

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Some β-mannans, including those in coffee bean and soy, contain a mannose backbone with β-(1→4) bonds. Such mannooligosaccharides could have immunological functions involving direct interaction with immune cells, in addition to acting as prebiotics. This study aimed at assessing the immunological function of mannooligosaccharides with β-(1→4) bond, and elucidating their mechanism of action using bone marrow-derived murine dendritic cells (BMDCs). When BMDCs were stimulated with the mannooligosaccharides, only β-Man-(1→4)-Man significantly induced production of cytokines that included IL-6, IL-10, TNF-α, and IFN-β, and enhanced CD4+ T-cell stimulatory capacity. Use of putative receptor inhibitors revealed the binding of β-Man-(1→4)-Man to TLR4/MD2 complex and involvement with the complement C3a receptor (C3aR) for BMDC activation. Interestingly, β-Man-(1→4)-Man prolonged the production of pro-inflammatory cytokines (IL-6 and TNF-α), but not of the IL-10 anti-inflammatory cytokine during extended culture of BMDCs, associated with high glucose consumption. The results suggest that β-Man-(1→4)-Man is an immunostimulatory molecule, and that the promotion of glycolysis could be involved in the production of pro-inflammatory cytokine in β-Man-(1→4)-Man-stimulated BMDCs. This study could contribute to development of immune-boosting functional foods and a novel vaccine adjuvant.

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NFκB- and MAP-Kinase Signaling Contribute to the Activation of Murine Myeloid Dendritic Cells by a Flagellin A: Allergen Fusion Protein

Cited by 18 publications

References 69 publications

Impact of Probiotic Bacteria on Respiratory Allergy Disorders

Impact of Probiotic Bacteria on Respiratory Allergy Disorders

Tropomodulin1 Expression Increases Upon Maturation in Dendritic Cells and Promotes Their Maturation and Immune Functions

β-(1→4)-Mannobiose Acts as an Immunostimulatory Molecule in Murine Dendritic Cells by Binding the TLR4/MD-2 Complex

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