4 results on '"Raymakers, Reinier A. P."'
Search Results
2. TLR4-mediated podosome loss discriminates gram-negative from gram-positive bacteria in their capacity to induce dendritic cell migration and maturation.
- Author
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van Helden SF, van den Dries K, Oud MM, Raymakers RA, Netea MG, van Leeuwen FN, and Figdor CG
- Subjects
- Animals, Cell Adhesion genetics, Cell Adhesion immunology, Cell Differentiation genetics, Dendritic Cells cytology, Gram-Negative Bacteria pathogenicity, Gram-Positive Bacteria pathogenicity, Meningococcal Infections immunology, Meningococcal Infections microbiology, Meningococcal Infections pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Pneumococcal Infections immunology, Pneumococcal Infections microbiology, Pneumococcal Infections pathology, Pseudopodia microbiology, Pseudopodia pathology, Salmonella Infections, Animal immunology, Salmonella Infections, Animal microbiology, Salmonella Infections, Animal pathology, Staphylococcal Infections immunology, Staphylococcal Infections microbiology, Staphylococcal Infections pathology, Toll-Like Receptor 4 deficiency, Toll-Like Receptor 4 genetics, Cell Differentiation immunology, Cell Movement immunology, Dendritic Cells immunology, Dendritic Cells microbiology, Gram-Negative Bacteria immunology, Gram-Positive Bacteria immunology, Pseudopodia immunology, Toll-Like Receptor 4 physiology
- Abstract
Chronic infections are caused by microorganisms that display effective immune evasion mechanisms. Dendritic cell (DC)-dependent T cell-mediated adaptive immunity is one of the mechanisms that have evolved to prevent the occurrence of chronic bacterial infections. In turn, bacterial pathogens have developed strategies to evade immune recognition. In this study, we show that gram-negative and gram-positive bacteria differ in their ability to activate DCs and that gram-negative bacteria are far more effective inducers of DC maturation. Moreover, we observed that only gram-negative bacteria can induce loss of adhesive podosome structures in DCs, a response necessary for the induction of effective DC migration. We demonstrate that the ability of gram-negative bacteria to trigger podosome turnover and induce DC migration reflects their capacity to selectively activate TLR4. Examining mice defective in TLR4 signaling, we show that this DC maturation and migration are mainly Toll/IL-1 receptor domain-containing adaptor-inducing IFNbeta-dependent. Furthermore, we show that these processes depend on the production of PGs by these DCs, suggesting a direct link between TLR4-mediated signaling and arachidonic metabolism. These findings demonstrate that gram-positive and gram-negative bacteria profoundly differ in their capacity to activate DCs. We propose that this inability of gram-positive bacteria to induce DC maturation and migration is part of the armamentarium necessary for avoiding the induction of an effective cellular immune response and may explain the frequent involvement of these pathogens in chronic infections.
- Published
- 2010
- Full Text
- View/download PDF
3. The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.
- Author
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van Spriel AB, Sofi M, Gartlan KH, van der Schaaf A, Verschueren I, Torensma R, Raymakers RA, Loveland BE, Netea MG, Adema GJ, Wright MD, and Figdor CG
- Subjects
- Animals, Antigens, CD genetics, Antigens, Neoplasm genetics, B-Lymphocytes cytology, B-Lymphocytes metabolism, Female, Flow Cytometry, Germinal Center immunology, Glycoproteins genetics, Humans, Immunoglobulin A biosynthesis, Immunohistochemistry, Interleukin-6 immunology, Interleukin-6 metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Tetraspanins, Antigens, CD immunology, Antigens, Neoplasm immunology, B-Lymphocytes immunology, Cell Differentiation immunology, Glycoproteins immunology, Immunoglobulin A immunology, Mycoses immunology
- Abstract
Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA(+) plasma cells remain poorly understood. Here, we report that the B cell-expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37-/-) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA(+) plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37-deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37-/- mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37-/- mice. To demonstrate the importance of CD37-which can associate with the pattern-recognition receptor dectin-1-in immunity to infection, CD37-/- mice were exposed to Candida albicans. We report that CD37-/- mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans-specific IgA antibodies. Importantly, adoptive transfer of CD37-/- serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response.
- Published
- 2009
- Full Text
- View/download PDF
4. A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation.
- Author
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van Helden SF, Krooshoop DJ, Broers KC, Raymakers RA, Figdor CG, and van Leeuwen FN
- Subjects
- Cell Adhesion immunology, Cell Surface Extensions immunology, Dinoprostone biosynthesis, Humans, Integrin alpha5beta1 antagonists & inhibitors, Integrin alpha5beta1 metabolism, Integrin alpha5beta1 physiology, Lipopolysaccharides pharmacology, Myeloid Progenitor Cells cytology, Myeloid Progenitor Cells metabolism, Signal Transduction immunology, Time Factors, Cell Differentiation immunology, Cell Movement immunology, Cell Surface Extensions metabolism, Dendritic Cells cytology, Dendritic Cells metabolism, Dinoprostone physiology
- Abstract
Dendritic cells (DCs) are professional APCs of the immune system that play a key role in regulating T cell-based immunity. The capacity of DCs to activate T cells depends on their maturation state as well as their ability to migrate to the T cell areas of draining lymph nodes. In this study, we investigated the effects of DC maturation stimuli on the actin cytoskeleton and beta(1) integrin-dependent adhesion and migration. Podosomes, specialized adhesion structures found in immature monocyte-derived DCs as well as myeloid DCs, rapidly dissolve in response to maturation stimuli such as TNF-alpha and PGE(2), whereas the TLR agonist LPS induces podosome dissolution only after a long lag time. We demonstrate that LPS-mediated podosome disassembly as well as the onset of high-speed DC migration are dependent on the production of PGs by the DCs. Moreover, both of these processes are inhibited by Ab-induced activation of beta(1) integrins. Together, these results show that maturation-induced podosome dissolution and loss of alpha(5)beta(1) integrin activity allow human DCs to undergo the transition from an adhesive to a highly migratory phenotype.
- Published
- 2006
- Full Text
- View/download PDF
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