Refine
Has Fulltext
- yes (25)
Is part of the Bibliography
- yes (25)
Year of publication
Document Type
- Journal article (25)
Language
- English (25)
Keywords
- T cells (4)
- dendritic cells (4)
- regulatory T cells (4)
- GM-CSF (2)
- Medizin (2)
- Parkinson’s disease (2)
- immune evasion (2)
- macrophages (2)
- monocytes (2)
- Allotransplantation (1)
- Alpha therapy (1)
- Aspergillus fumigatus (1)
- Autoimmune diseases (1)
- BCG (1)
- Bone marrow transplantantation (1)
- Brugia Malayi (1)
- CD39 (1)
- CD73 (1)
- DAPI staining (1)
- Dendritic cells (1)
- Dendritische Zelle (1)
- Expression (1)
- Factor receptor (1)
- Flt3L (1)
- Graft-versus-leukemia (1)
- IL-2 (1)
- IL-3 (1)
- IL‐10 (1)
- Immunology (1)
- Immunosuppression (1)
- Infectious disease (1)
- LIF (1)
- Langerhans cells (1)
- Mesocestoides corti (1)
- Monocytes and macrophages (1)
- Multiple myeloma (1)
- Mycobacterium tuberculosis (1)
- Regulatory T cells (1)
- Regulatory-cells (1)
- RelB (1)
- Rheumatoid arthritis (1)
- Suppression (1)
- T Cells (1)
- T cell suppression (1)
- T helper cell responses (1)
- TGF-BETA (1)
- TLR2 (1)
- TLR4 (1)
- TNF-alpha (1)
- Tr1 (1)
- Tumor-necrosis-factor (1)
- VLA-1 (1)
- adenosine (1)
- alveoar echinococcosis (1)
- anergy (1)
- antigen-B (1)
- aorta (1)
- bacteria (1)
- bone marrow (1)
- cDC2 subset (1)
- caveolin-1 (Cav-1) (1)
- cell differentiation (1)
- cell staining (1)
- cholera (1)
- conversion (1)
- cytokines (1)
- diet (1)
- epicutaneous (1)
- excretory-secretory (1)
- flow cytometry (1)
- fungal infection (1)
- gene expression (1)
- granulosus (1)
- helminths (1)
- homing (1)
- host-pathogen interactions (1)
- humans (1)
- hydatid disease (1)
- immune control (1)
- immune escape (1)
- immune response (1)
- immunoprecipitation (1)
- in vitro culture (1)
- in vivo (1)
- innate immune response (1)
- larvae (1)
- lymph nodes (1)
- metacestode vesicles (1)
- migration (1)
- murine model (1)
- mycobacteria (1)
- myeloid-derived suppressor cell (MDSC) (1)
- myeloid-derived suppressor cells (MDSC) (1)
- myeloid-derived suppressor cells (MDSCs) (1)
- neurodegeneration (1)
- neuroinflammation (1)
- neuroprotection (1)
- ovarian cancer (1)
- parasitic diseases (1)
- primary cells (1)
- proteomic analysis (1)
- protocol (1)
- small interfering RNAs (1)
- spleen (1)
- steady state (1)
- steady-state dendritic cells (1)
- tolerance (1)
- tolerogenic dendritic cells (1)
- toxins (1)
- transcriptional profiling (1)
- transcutaneous (1)
- transient regulatory T-cell targeting (1)
- tumor associated macrophages (1)
- vesicles (1)
- α-synuclein-specific T cells (1)
Institute
- Institut für Virologie und Immunbiologie (25)
- Medizinische Klinik und Poliklinik II (5)
- Institut für Hygiene und Mikrobiologie (3)
- Julius-von-Sachs-Institut für Biowissenschaften (2)
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie (2)
- Neurologische Klinik und Poliklinik (2)
- Pathologisches Institut (2)
- Theodor-Boveri-Institut für Biowissenschaften (2)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (1)
- Frauenklinik und Poliklinik (1)
EU-Project number / Contract (GA) number
- 825575 (1)
Background
Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases. Although 99% of individuals infected with Mtb develop a CD4+ Th1 and CD8+ T cell mediated immunity as measured by tuberculin skin test, this results only in partial protection and Mtb vaccines are not effective. Deviation of immune responses by pathogens towards a Th2 profile is a common mechanism of immune evasion, typically leading to the persistence of the microbes.
Results
Here we tested the stimulatory capacity of selective Mtb antigens on human monocyte-derived dendritic cell (DC) maturation and cytokine production. DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers. All Mtb antigens induced variable levels of IL-6 and low levels of IL-10, there was no release of IL-12p70 detectable. Substantial IL-12p40 production was restricted to LPS or H37Ra and H37Rv preparations. Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4+ T cells after secondary stimulation as compared to H37Ra and H37Rv preparations.
Conclusion
Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.
Background: Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC) are key effectors in shaping the immune response and among the first cells encountered by the parasite during an infection. Although it is assumed that E. multilocularis, by excretory/secretory (E/S)-products, specifically affects DC to deviate immune responses, little information is available on the molecular nature of respective E/S-products and their mode of action. Methodology/Principal Findings: We established cultivation systems for exposing DC to live material from early (oncosphere), chronic (metacestode) and late (protoscolex) infectious stages. When co-incubated with Echinococcus primary cells, representing the invading oncosphere, or metacestode vesicles, a significant proportion of DC underwent apoptosis and the surviving DC failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation markers and did not undergo apoptosis. After pre-incubation with primary cells and metacestode vesicles, DC showed a strongly impaired ability to be activated by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex E/S-products. While none of the larvae induced the secretion of pro-inflammatory IL-12p70, the production of immunosuppressive IL-10 was elevated in response to primary cell E/S-products. Finally, upon incubation with DC and naive T-cells, E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T cells in vitro. Conclusions: This is the first report on the induction of apoptosis in DC by cestode E/S-products. Our data indicate that the early infective stage of E. multilocularis is a strong inducer of tolerance in DC, which is most probably important for generating an immunosuppressive environment at an infection phase in which the parasite is highly vulnerable to host attacks. The induction of CD4+CD25+Foxp3+ T cells through metacestode E/S-products suggests that these cells fulfill an important role for parasite persistence during chronic echinococcosis.
The ability of CD4+Foxp3+ regulatory T-cells (Treg) to produce interleukin (IL)-10 is important for the limitation of inflammation at environmental interfaces like colon or lung. Under steady state conditions, however, few Tregs produce IL-10 ex vivo. To investigate the origin and fate of IL-10 producing Tregs we used a superagonistic mouse anti-mouse CD28 mAb (CD28SA) for polyclonal in vivo stimulation of Tregs, which not only led to their numeric expansion but also to a dramatic increase in IL-10 production. IL-10 secreting Tregs strongly upregulated surface receptors associated with suppressive function as compared to non-producing Tregs. Furthermore, polyclonally expanding Tregs shifted their migration receptor pattern after activation from a CCR7+CCR52 lymph node-seeking to a CCR72CCR5+ inflammationseeking phenotype, explaining the preferential recruitment of IL-10 producers to sites of ongoing immune responses. Finally, we observed that IL-10 producing Tregs from CD28SA stimulated mice were more apoptosis-prone in vitro than their IL-10 negative counterparts. These findings support a model where prolonged activation of Tregs results in terminal differentiation towards an IL-10 producing effector phenotype associated with a limited lifespan, implicating built-in termination of immunosuppression.
Dendritic cells (DCs) are major players in the control of adaptive tolerance and immunity. Therefore, their specific generation and adoptive transfer into patients or their in vivo targeting is attractive for clinical applications. While injections of mature immunogenic DCs are tested in clinical trials, tolerogenic DCs still are awaiting this step. Besides the tolerogenic potential of immature DCs, also semi-mature DCs can show tolerogenic activity but both types also bear unfavorable features. Optimal tolerogenic DCs, their molecular tool bar, and their use for specific diseases still have to be defined. Here, the usefulness of in vitro generated and adoptively transferred semi-mature DCs for tolerance induction is outlined. The in vivo targeting of semi-mature DCs as represented by steady state migratory DCs are discussed for treatment of autoimmune diseases and allergies. First clinical trials with transcutaneous allergen application may point to their therapeutic use in the future.
Background: Dendritic cells (DC) can act tolerogenic at a semi-mature stage by induction of protective CD4+ T cell and NKT cell responses. Methodology/Principal Findings: Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semimature DC that were generated from bone marrow (BM) cells of B7-H12/2 mice and applied to the model of Experimental Autoimmune Encephalomyelitis (EAE). Injections of B7-H1-deficient DC showed increased EAE protection as compared to wild type (WT)-DC. Injections of B7-H12/2 TNF-DC induced higher release of peptide-specific IL-10 and IL-13 after restimulation in vitro together with elevated serum cytokines IL-4 and IL-13 produced by NKT cells, and reduced IL-17 and IFN-c production in the CNS. Experiments in CD1d2/2 and Ja2812/2 mice as well as with type I and II NKT cell lines indicated that only type II NKT cells but not type I NKT cells (invariant NKT cells) could be stimulated by an endogenous CD1d-ligand on DC and were responsible for the increased serum cytokine production in the absence of B7-H1. Conclusions/Significance: Together, our data indicate that BM-DC express an endogenous CD1d ligand and B7-H1 to ihibit type II but not type I NKT cells. In the absence of B7-H1 on these DC their tolerogenic potential to stimulate tolerogenic CD4+ and NKT cell responses is enhanced.