56 results on '"Joosten, Ben"'
Search Results
52. Interleukin-4 Alters Early Phagosome Phenotype by Modulating Class I PI3K Dependent Lipid Remodeling and Protein Recruitment.
- Author
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De Keijzer, Sandra, Meddens, Marjolein B. M., Kilic, Dilek, Joosten, Ben, Reinieren-Beeren, Inge, Lidke, Diane S., and Cambi, Alessandra
- Subjects
INTERLEUKIN-4 ,PHAGOSOMES ,PHENOTYPES ,PHOSPHOINOSITIDES ,MACROPHAGES ,CONFOCAL microscopy ,BIOLOGICAL membranes - Abstract
Phagocytosis is a complex process that involves membranelipid remodeling and the attraction and retention of key effector proteins. Phagosome phenotype depends on the type of receptor engaged and can be influenced by extracellular signals. Interleukin 4 (IL-4) is a cytokine that induces the alternative activation of macrophages (MWs) upon prolonged exposure, triggering a different cell phenotype that has an altered phagocytic capacity. In contrast, the direct effects of IL-4 during phagocytosis remain unknown. Here, we investigate the impact of short-termIL-4 exposure (1 hour) during phagocytosis of IgGopsonized yeast particles by MWs. By time-lapse confocal microscopy of GFP-tagged lipid-sensing probes, we show that IL-4 increases the negative charge of the phagosomal membrane by prolonging the presence of the negatively charged second messenger PI(3,4,5)P3. Biochemical assays reveal an enhanced PI3K/Akt activity upon phagocytosis in the presence of IL-4. Blocking the specific class I PI3K after the onset of phagocytosis completely abrogates the IL-4-induced changes in lipid remodeling and concomitant membrane charge. Finally, we show that IL-4 direct signaling leads to a significantly prolonged retention profile of the signaling molecules Rac1 and Rab5 to the phagosomal membrane in a PI3K-dependent manner. This protracted early phagosome phenotype suggests an altered maturation, which is supported by the delayed phagosome acidification measured in the presence of IL-4. Our findings reveal that molecular differences in IL-4 levels, in the extracellular microenvironment, influence the coordination of lipid remodeling and protein recruitment, which determine phagosome phenotype and, eventually, fate. Endosomal and phagosomalmembranes provide topological constraints to signalingmolecules. Therefore, changes in the phagosome phenotype modulated by extracellular factors may represent an additional mechanism that regulates the outcome of phagocytosis and could have significant impact on the net biochemical output of a cell. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
53. The C-type lectin DC-SIGN internalizes soluble antigens and HIV-1 virions via a clathrin-dependent mechanism.
- Author
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Cambi, Alessandra, Beeren, Inge, Joosten, Ben, Fransen, Jack A., and Figdor, Carl G.
- Abstract
Dendritic cells (DC), professional Ag-presenting cells located in mucosae and lymphoid organs, operate at the interface of innate and adaptive immunity and are likely the first cells to encounter invading HIV-1. Although the C-type lectin DC-Specific ICAM-3-grabbing non-integrin (DC-SIGN) binds to several viruses, including HIV-1, its direct involvement in viral entry remains controversial. Despite its central role in DC function, little is known about the underlying molecular mechanism(s) of DC-SIGN-mediated Ag uptake. Here, we analyzed the early stages of DC-SIGN-mediated endocytosis and demonstrate that both membrane cholesterol and dynamin are required. Confocal microscopy and clathrin RNAi showed that DC-SIGN-mediated internalization occurs via clathrin-coated pits. Electron microscopy of ultrathin sections showed the involvement of DC-SIGN in clathrin-dependent HIV-1 internalization by DC. Currently, DC-specific C-type lectins are considered potential target in anti-tumor clinical trials. Detailed information about how different Ag are internalized via these receptors will facilitate the rational design of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
54. DCIR is endocytosed into human dendritic cells and inhibits TLR8‐mediated cytokine production
- Author
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Meyer‐Wentrup, Friederike, Cambi, Alessandra, Joosten, Ben, Looman, Maaike W., Vries, I. Jolanda M., Figdor, Carl G., and Adema, Gosse J.
- Abstract
C‐type lectin receptors (CLRs) expressed on APCs play a pivotal role in the immune system as pattern‐recognition and antigen‐uptake receptors. In addition, they may signal directly, leading to cytokine production and immune modulation. To this end, some CLRs, like dectin‐1 and dendritic cell immunoreceptor (DCIR), contain intracellular ITIMs or ITAMs. In this study, we explored expression and function of the ITIM‐containing CLR DCIR on professional APCs. DCIR is expressed on immature and mature monocyte‐derived DCs (moDC) but also on monocytes, macrophages, B cells, and freshly isolated myeloid and plasmacytoid DCs. We show that endogenous DCIR is internalized efficiently into human moDC after triggering with DCIR‐specific mAb. DCIR internalization is clathrin‐dependent and leads to its localization in the endo‐/lysosomal compartment, including lysosome‐associated membrane protein‐1+ lysosomes. DCIR triggering affected neither TLR4‐ nor TLR8‐mediated CD80 and CD86 up‐regulation. Interestingly, it did inhibit TLR8‐mediated IL‐12 and TNF‐α production significantly, and TLR2‐, TLR3‐, or TLR4‐induced cytokine production was not affected. Collectively, the data presented characterize DCIR as an APC receptor that is endocytosed efficiently in a clathrin‐dependent manner and negatively affects TLR8‐mediated cytokine production. These data provide further support to the concept of CLR/TLR cross‐talk in modulating immune responses.
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- 2009
- Full Text
- View/download PDF
55. Relevance of DC‐SIGN in DC‐induced T cell proliferation
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Gijzen, Karlijn, Tacken, Paul J., Zimmerman, Aukje, Joosten, Ben, Vries, I. Jolanda M., Figdor, Carl G., and Torensma, Ruurd
- Abstract
The role of dendritic cell‐specific ICAM‐3‐grabbing nonintegrin (DC‐SIGN) in DC‐T cell communication was assessed by analyzing the effect of DC‐SIGN‐blocking mAb in MLR. The results show that the degree of inhibition by DC‐SIGN and LFA‐1 mAb depends on the magnitude of the MLR and the maturation status of the DC. Addition of DC‐SIGN mAb at several time‐points during MLR showed that DC‐SIGN is involved early on in DC‐T cell contacts. This initial role is masked by strong adhesive and costimulatory mechanisms, indicating a short‐lived effect of DC‐SIGN in DC‐T cell interactions. To examine this concept in more detail, the percentage of PBL capable of binding DC‐SIGN was determined. Analysis of several donors revealed that 1–20% PBL bind to beads coated with recombinant DC‐SIGN, and the DC‐SIGN‐binding cells comprised all major cell subsets found in blood. PBL isolated from a donor with high DC‐SIGN‐binding capacity were more prone to blocking by DC‐SIGN mAb in MLR than PBL from a donor with low DC‐SIGN‐binding capacity. This study indicates an initial and transient role for DC‐SIGN in T cell proliferation, which becomes apparent when T cell proliferation is low and when the percentage of DC‐SIGN binding PBL is high.
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- 2007
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56. PGE2-mediated podosome loss in dendritic cells is dependent on actomyosin contraction downstream of the RhoA--Rho-kinase axis.
- Author
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Van Helden, Suzanne F. G., Oud, Machteld M., Joosten, Ben, Peterse, Niels, Figdor, Carl G., and Van Leeuwen, Frank N.
- Subjects
DENDRITIC cells ,CONTRACTILITY (Biology) ,ACTOMYOSIN ,RHO GTPases ,INFLAMMATORY mediators - Abstract
Podosomes are dynamic adhesion structures found in dendritic cells (DCs) and other cells of the myeloid lineage. We previously showed that prostaglandin E2 (PGE
2 ), an important proinflammatory mediator produced during DC maturation, induces podosome disassembly within minutes after stimulation. Here, we demonstrate that this response is mediated by cAMP elevation, occurs downstream of Rho kinase and is dependent on myosin II. Whereas PGE2 stimulation leads to activation of the small GTPase RhoA, decreased levels of Rac1-GTP and Cdc42-GTP are observed. These results show that PGE2 stimulation leads to activation of the RhoA Rho-kinase axis to promote actomyosin-based contraction and subsequent podosome dissolution. Because podosome disassembly is accompanied by de novo formation of focal adhesions, we propose that the disassembly/formation of these two different adhesion structures is oppositely regulated by actomyosin contractility and relative activities of RhoA, Rac1 and Cdc42. [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
- View/download PDF
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