Research Topics
Genomes and Genes | B J KullbergSummaryAffiliation: Radboud University Nijmegen Medical Centre Country: The Netherlands Publications
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Publications
Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohortsOliver Kumpf
Department of Anesthesiology, Intensive Care Medicine and Pain Management, HANSE Klinikum Stralsund, Grosse Parower Strasse 47 53, Stralsund 18435, Germany
Crit Care 14:R103. 2010....
[Dutch Health Council advice 'Vaccination against pneumococcal infections in elderly persons and immunocompromised adults']B J Kullberg
Universitair Medisch Centrum St Radboud, afd Algemeen Interne Geneeskunde huispost 541, Postbus 9101, 6500 HB Nijmegen
Ned Tijdschr Geneeskd 148:871-4. 2004....
Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trialB J Kullberg
Nijmegen University Centre for Infectious Diseases, Department of Internal Medicine 484, Radboud University Nijmegen Medical Centre 541, PO Box 9101, 6500 HB Nijmegen, Netherlands
Lancet 366:1435-42. 2005..This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients...
[Invasive zygomycosis: notably in diabetes mellitus and iron overload]B J Kullberg
Universitair Medisch Centrum St Radboud, Nijmeegs Universitair Centrum voor Infectieziekten, Nijmegen
Ned Tijdschr Geneeskd 151:2603-5. 2007..Rapid diagnosis, reversal of the underlying predisposition and timely surgical debridement are the underlying principles of therapy for this disease...
Design of efficacy trials of cytokines in combination with antifungal drugsBart Jan Kullberg
Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
Clin Infect Dis 39:S218-23. 2004....
Severe acute respiratory syndrome: lessons and uncertaintiesB J Kullberg
Departments of Medicine, University Medical Centre St Radboud, Nijmegen, The Netherlands
Neth J Med 61:235-7. 2003..The source of the outbreak and the exact modes of transmission are still subjects of research. Important lessons can be learned from the SARS outbreak about both the scientific and the public health approach to emerging pathogens...
European expert opinion on the management of invasive candidiasis in adultsB J Kullberg
Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Clin Microbiol Infect 17:1-12. 2011....
Interleukin-18 induces production of proinflammatory cytokines in mice: no intermediate role for the cytokines of the tumor necrosis factor family and interleukin-1betaM G Netea
Department of Medicine, University Hospital Nijmegen, The Netherlands
Eur J Immunol 30:3057-60. 2000....
Recombinant murine granulocyte colony-stimulating factor protects against acute disseminated Candida albicans infection in nonneutropenic miceB J Kullberg
Department of Medicine, Catholic University Nijmegen and University Hospital, The Netherlands
J Infect Dis 177:175-81. 1998..These results indicate that rG-CSF enhances host resistance to disseminated candidiasis in nonneutropenic mice through activation of granulocytes and their recruitment to the site of infection...
Lethal Escherichia coli and Salmonella typhimurium endotoxemia is mediated through different pathwaysM G Netea
Division of General Internal Medicine, Department of Medicine, Nijmegen University Medical Center, Nijmegen, The Netherlands
Eur J Immunol 31:2529-38. 2001..In conclusion, TNF and LT play a central role in the lethality due to E. coli LPS, whereas the lethal effects of S. typhimurium LPS are mediated through mechanisms also involving other cytokines such as IFN-gamma, IL-1 and IL-18...
Crystals of monosodium urate monohydrate enhance lipopolysaccharide-induced release of interleukin 1 beta by mononuclear cells through a caspase 1-mediated processE J Giamarellos-Bourboulis
Department of Internal Medicine, University Medical Centre St Radboud, Nijmegen, The Netherlands
Ann Rheum Dis 68:273-8. 2009..In the present study we have investigated whether production of proinflammatory cytokines by crystals was exacerbated during costimulation with Toll-like receptor (TLR) ligands...
[Optimizing the antibiotics policy in The Netherlands. VIII. Revised SWAB guidelines for antimicrobial therapy in adults with community-acquired pneumonia]J A Schouten
Universitair Medisch Centrum St Radboud, Nijmeegs Universitair Centrum voor Infectieziekten, afd. Algemeen Interne Geneeskunde, Postbus 9101, 6500 HB Nijmegen
Ned Tijdschr Geneeskd 149:2495-500. 2005..Empirical therapy should be replaced with pathogen-directed therapy if the causative agent is identified...
Milder clinical hyperimmunoglobulin E syndrome phenotype is associated with partial interleukin-17 deficiencyF L van de Veerdonk
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Clin Exp Immunol 159:57-64. 2010..These data demonstrate that defective IL-17 production in response to specific pathogens can differ between patients with HIES and that the extent of the defective Th17 response determines their clinical phenotype...
Aspergillus meningitis: diagnosis by non-culture-based microbiological methods and managementP E Verweij
Departments of Medical Microbiology, University Hospital Nijmegen, Nijmegen, The Netherlands
J Clin Microbiol 37:1186-9. 1999..Decline of the galactomannan antigen titer in the CSF during treatment with intravenous and intraventricular amphotericin B and intravenous voriconazole corresponded with the clinical response to treatment...
Recognition of fungal pathogens by Toll-like receptorsM G Netea
Department of Medicine, Radboud University Medical Center Nijmegen, Geert Grooteplein 8, P O Box 9101, Nijmegen, The Netherlands
Eur J Clin Microbiol Infect Dis 23:672-6. 2004..These new data have substantially increased our knowledge of the recognition of fungal pathogens, and the study of TLRs remains one of the most active areas of research in the field of fungal infections...
Use of fluconazole in daily practice: still room for improvementS Natsch
Department of General Internal Medicine, University Medical Center, Nijmegen, The Netherlands
J Antimicrob Chemother 48:303-10. 2001..However, important issues for improvement could be identified, such as increasing the dosage and duration of treatment in cases of serious infections, and withholding treatment from patients with colonization rather than infection...
Candida-specific interferon-gamma deficiency and toll-like receptor polymorphisms in patients with chronic mucocutaneous candidiasisC A A van der Graaf
Department of Internal Medicine (541, University Medical Centre St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Neth J Med 61:365-9. 2003..These data support the hypothesis that deficient IFNgamma production is involved in the pathogenesis of CMC, whereas a role for genetic polymorphisms of Toll-like receptor 2 and 4 is not obvious in these patients...
An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasisA M L Oude Lashof
Nijmegen University Medical Center, St Radboud and Nijmegen University, Center for Infectious Diseases, Nijmegen, The Netherlands
Eur J Cancer 40:1314-9. 2004..This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole...
Quality of antibiotic use for lower respiratory tract infections at hospitals: (how) can we measure it?J A Schouten
Centre for Quality of Care Research, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Clin Infect Dis 41:450-60. 2005..This set should also be applicable in practice...
Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitusG R C Zilverschoon
Department of General Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Int J Obes (Lond) 32:1407-14. 2008..Paradoxically, concentrations of circulating IL-18 in obese subjects and in patients with type 2 diabetes are increased. The objective of this study is to provide an explanation for this paradox...
Acellular components of Chlamydia pneumoniae stimulate cytokine production in human blood mononuclear cellsM G Netea
Department of Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands
Eur J Immunol 30:541-9. 2000..In conclusion, acellular components of C. pneumoniae are a potent stimulus for cytokine production, and this mechanism may have an important role in the inflammatory aspects of atherogenesis...
Severely impaired IL-12/IL-18/IFNgamma axis in patients with hyper IgE syndromeM G Netea
Radboud University Medical Centre and Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands
Eur J Clin Invest 35:718-21. 2005..CONCLUSIONS: These data revealed a severe dysbalance towards a Th2 phenotype in HIES patients which is likely to contribute to the specific pattern of infection susceptibility characteristic to HIES...
Two cases of subcutaneous Scedosporium apiospermum infection treated with voriconazoleF Bosma
Department of Medical Microbiology, University Medical Center Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
Clin Microbiol Infect 9:750-3. 2003..apiospermum, and random amplified polymorphic DNA (RAPD) fingerprinting showed that the patients' strains were genotypically unrelated, we considered a common nosocomial source of S. apiospermum to be unlikely...
Role of the dual interaction of fungal pathogens with pattern recognition receptors in the activation and modulation of host defenceM G Netea
Department of Medicine, Radboud University Nijmegen Medical Center, and Nijmegen University Center for Infectious Diseases, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands
Clin Microbiol Infect 12:404-9. 2006..Thus, signals mediated by recognition receptors are not only beneficial to the host, but in certain situations can be used by pathogenic fungi to escape immune recognition and promote infection...
[Improved diagnostics in invasive aspergillosis and systematic monitoring in patients at high risk of infection]P E Verweij
Universitair Medisch Centrum St Radboud, Nijmeegs Universitair Centrum voor Infectieziekten, Postbus 91o1, 6500 HB, Nijmegen
Ned Tijdschr Geneeskd 149:561-7. 2005..The pre-emptive management strategy which combines monitoring of patients for surrogate markers with a HRCT scan appears to be a promising approach to the early identification and treatment of patients with invasive aspergillosis...
Increased voluntary exercise in mice deficient for tumour necrosis factor-alpha and lymphotoxin-alphaM G Netea
Department of Medicine, Nijmegen University Centre for Infectious Diseases, Nijmegen, The Netherlands
Eur J Clin Invest 37:737-41. 2007..We hypothesized that proinflammatory cytokines, in particular tumour necrosis factor-alpha (TNFalpha) and lymphotoxin-alpha (LT) transmit signals leading to fatigue...
Q fever in the Netherlands from 2007 to 2010C E Delsing
Department of Internal Medicine Radboud Expertise Centre for Q fever, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Neth J Med 68:382-7. 2010..Finally, the latest data on clinical presentation and diagnostic and therapeutic dilemmas of Q fever in the Netherlands are reviewed...
NOD2 3020insC mutation and the pathogenesis of Crohn's disease: impaired IL-1beta production points to a loss-of-function phenotypeM G Netea
Departments of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Neth J Med 63:305-8. 2005..e. a gain of function. In previous papers we proposed the former, since we could show decreased cytokine production with a net proinflammatory status after exposure to muramyl dipeptide (MDP)...
Revised SWAB guidelines for antimicrobial therapy of community-acquired pneumoniaJ A Schouten
Nijmegen University Centre for Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Neth J Med 63:323-35. 2005..The Legionella urine antigen test plays an important role in decisions on the choice of initial antibiotic treatment...
[Amphotericin B: the end of an era]A M L Oude Lashof
Universitair Medisch Centrum St Radboud, Nijmeegs Universitair Centrum voor Infectieziekten, afd. Algemeen Interne Geneeskunde AIG-541, Postbus 9101, 6500 HB Nijmegen
Ned Tijdschr Geneeskd 148:1665-8. 2004..The current armamentarium of azoles and echinocandins for the treatment of invasive mycoses has only left a very minor role for both conventional and lipid-associated amphotericin B in the treatment of a few specific, rare mycoses...
Increased susceptibility of TNF-alpha lymphotoxin-alpha double knockout mice to systemic candidiasis through impaired recruitment of neutrophils and phagocytosis of Candida albicansM G Netea
Department of Medicine, University Hospital Nijmegen, The Netherlands
J Immunol 163:1498-505. 1999..albicans...
Chronic yersiniosis due to defects in the TLR5 and NOD2 recognition pathwaysM G Netea
Nijmegen University Centre for Infectious Diseases, Nijmegen, The Netherlands
Neth J Med 68:310-5. 2010..In conclusion, we describe a patient in whom specific defects in the TLR5 and NOD2 recognition pathways led to chronic yersiniosis...
Diagnosis of Candida lung abscesses by 18F-fluorodeoxyglucose positron emission tomographyC P Bleeker-Rovers
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Clin Microbiol Infect 11:493-5. 2005..It was concluded that FDG-PET is a promising new imaging technique that enables early identification of sites of disseminated candidiasis, and that this technique can be used in the evaluation of therapy...
Reduced adrenal response and increased mortality after systemic Klebsiella pneumoniae infection in interleukin-6-deficient miceF H van Enckevort
Department of Endocrinology 531, Nijmegen University Medical Center, P O Box 9101, 6500 HB Nijmegen, The Netherlands
Eur Cytokine Netw 12:581-6. 2001..Furthermore, the reduced adrenal response may be an explanation for the strong inflammatory response with higher TNF-alpha plasma levels in IL-6-/- mice...
FDG-PET for imaging of non-osseous infection and inflammationF J Vos
Department of Internal Medicine, Nijmegen Medical Centre, Radboud University, Nijmegen, The Netherlands
Q J Nucl Med Mol Imaging 50:121-30. 2006....
Endocarditis: effects of routine echocardiography during Gram-positive bacteraemiaF J Vos
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Neth J Med 69:335-40. 2011..The aim of this study was to evaluate whether a regime including routine echocardiography results in better outcome...
Duration of antifungal treatment and development of delayed complications in patients with candidaemiaA M L Oude Lashof
Nijmegen University Centre for Infectious Diseases, Nijmegen University Medical Centre St. Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Eur J Clin Microbiol Infect Dis 22:43-8. 2003..This suggests that treatment of 2 weeks or less may be sufficient, provided the initial response to therapy is favourable...
Recurrent erysipelas despite antibiotic prophylaxis: an analysis from case studiesJ B Koster
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen University Centre for Infectious Diseases, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Neth J Med 65:89-94. 2007..A substantial proportion of patients experience recurrences of erysipelas, and this may be a reason to install prophylactic antibiotic treatment. Despite such prophylaxis, further recurrences are occasionally encountered...
Recognition of pathogenic microorganisms by Toll-like receptorsM G Netea
Department of Medicine, Radboud University Medical Center, Nijmegen, and Nijmegen University Center for Infectious Diseases, The Netherlands
Drugs Today (Barc) 42:99-105. 2006..These new data have substantially increased our knowledge of the recognition of microbial pathogens, and this remains one of the most active areas of research in the field of infectious diseases...
Defective interferon-gamma production in patients with hairy cell leukaemiaM G Netea
Division of General Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Neth J Med 66:340-34. 2008..Although several abnormalities of T-cell populations have been described in HCL, the effector mechanism responsible for the increased susceptibility to infections is not known...
Adjunctive immunotherapy with recombinant cytokines for the treatment of disseminated candidiasisF L van de Veerdonk
Nijmegen University Centre for Infectious Diseases, and Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Clin Microbiol Infect 18:112-9. 2012....
Adherence to local hospital guidelines for surgical antimicrobial prophylaxis: a multicentre audit in Dutch hospitalsM E E van Kasteren
Department of Internal Medicine 541, University Medical Centre Nijmegen, and Nijmegen University Centre for Infectious Diseases, P O Box 9101, 6500 HB Nijmegen, The Netherlands
J Antimicrob Chemother 51:1389-96. 2003..To study the adherence to local hospital guidelines for antimicrobial prophylaxis in surgery, and explore reasons for non-adherence...
Toll-like receptor-4 Asp299Gly polymorphism does not influence progression of atherosclerosis in patients with familial hypercholesterolaemiaM G Netea
University Medical Center, St Radboud, Nijmegen, The Netherlands
Eur J Clin Invest 34:94-9. 2004..We have investigated whether the presence of the Asp299Gly polymorphism in patients with familial hypercholesterolaemia (FH) has a similar protective effect, and whether it influences the effects of HMG-CoA reductase treatment...
Q fever in the Netherlands: a concise overview and implications of the largest ongoing outbreakC E Delsing
Department of General Internal Medicine and Nijmegen University Centre for Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Neth J Med 66:365-7. 2008..Treatment of community-acquired pneumonia has to take possible Q fever into account, and the high incidence of Q fever endocarditis and other manifestations of chronic Q fever require a specific diagnostic and therapeutic approach...
The impact of caspase-12 on susceptibility to candidemiaD C Rosentul
Department of Medicine, Radboud University Nijmegen Medical Centre, internal postal code 463, P O Box 9101, Geert Grooteplein 8, 6500 HB, Nijmegen, The Netherlands
Eur J Clin Microbiol Infect Dis 31:277-80. 2012..Although the functional CASPASE-12 allele has been suggested to increase susceptibility to bacterial sepsis, this could not be confirmed in our larger cohort of fungal sepsis patients...
Hyperlipoproteinemia enhances susceptibility to acute disseminated Candida albicans infection in low-density-lipoprotein-receptor-deficient miceM G Netea
Department of Medicine, University Hospital Nijmegen, The Netherlands
Infect Immun 65:2663-7. 1997..This latter phenomenon was probably due to increased binding of yeast cells to macrophages of LDLR-/- mice. These data suggest that hyperlipoproteinemia is deleterious in systemic candidiasis...
Internal medicine residents' knowledge about sepsis: effects of a teaching interventionM Tromp
Nijmegen Institute for Infection, Inflammation, and Immunity N4i, Radboud University Nijmegen Medical Centre, The Netherlands
Neth J Med 67:312-5. 2009..0001 compared with test 1), resulting in a mean score of 7.6 +/- 1.1. Our single teaching intervention resulted in improved and sustained knowledge on the assessment of symptoms, diagnosis and treatment of sepsis...
Selecting outcome parameters in studies aimed at improving rational use of antibiotics - practical considerationsS Natsch
Department of Clinical Pharmacy, University Medical Center Nijmegen, Nijmegen, The Netherlands
J Clin Pharm Ther 28:475-8. 2003..The essential point is the appropriate choice of outcome measure for the study. Examples drawn from the field of quality of use of antimicrobial drugs are discussed...
Complicating infectious foci in patients with Staphylococcus aureus or Streptococcus species bacteraemiaM L H Cuijpers
Department of Internal Medicine, 463, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500 HB, Nijmegen, The Netherlands
Eur J Clin Microbiol Infect Dis 26:105-13. 2007....
Low-density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe gram-negative infectionsM G Netea
Department of Medicine, University Hospital Nijmegen, The Netherlands
J Clin Invest 97:1366-72. 1996..At least part of this protection is achieved through decreased in vivo production of pro-inflammatory cytokines, in spite of increased cytokine production capacity...
Immune recognition of Candida albicans beta-glucan by dectin-1Neil A R Gow
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom
J Infect Dis 196:1565-71. 2007..albicans was independent of the recognition of beta-glucans by dectin-1. In conclusion, C. albicans induces production of monocyte-derived and T cell-derived cytokines through distinct pathways dependent on or independent of dectin-1...
Endoplasmic reticulum alpha-glycosidases of Candida albicans are required for N glycosylation, cell wall integrity, and normal host-fungus interactionHector M Mora Montes
Instituto de Investigacion en Biologia Experimental, Facultad de Quimica, Universidad de Guanajuato, Apartado Postal 187, Guanajuato, Gto CP 36000, Mexico
Eukaryot Cell 6:2184-93. 2007..Therefore, N-oligosaccharide processing by ER glycosidases is required for cell wall integrity and for host-fungus interactions...
Delayed clearance of intraabdominal abscesses caused by Candida albicans in tumor necrosis factor-alpha- and lymphotoxin-alpha-deficient miceAlieke G Vonk
Nijmegen University Center for Infectious Diseases and Department of Medicine, Nijmegen, The Netherlands
J Infect Dis 186:1815-22. 2002..In conclusion, TNF and LT are critical to the stimulation of effector cells that leads to elimination of Candida from abscesses...
Bartonella quintana lipopolysaccharide is a natural antagonist of Toll-like receptor 4Calin Popa
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, The Netherlands
Infect Immun 75:4831-7. 2007..Because of the role of TLR4 in inflammation, B. quintana LPS may prove useful as a potent anti-TLR4 agent with therapeutic potential in both infections and autoimmune inflammation...
Native LDL potentiate TNF alpha and IL-8 production by human mononuclear cellsMihai G Netea
Department of Medicine, University Medical Center St Radboud, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands Biochemistry, University Medical Center St Radboud, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands
J Lipid Res 43:1065-71. 2002..This may represent an important pathogenetic mechanism in atherogenesis induced by hyperlipoproteinemia...
Regulation of Staphylococcus epidermidis-induced IFN-gamma in whole human blood: the role of endogenous IL-18, IL-12, IL-1, and TNFRogier J L Stuyt
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA
Cytokine 21:65-73. 2003..In conclusion, S. epidermidis stimulates IFN-gamma which is IL-18, IL-12 and TNF-dependent, but IL-1 independent...
Recognition of fungal pathogens by toll-like receptorsMihai G Netea
Department of Medicine, Radboud University Nijmegen Medical Center, and Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands
Curr Pharm Des 12:4195-201. 2006..These recent developments provide crucial information for understanding the mechanisms of fungal recognition by cells of the immune system, and provide hope for designing new therapeutical approaches to fungal infections...
Host defence against disseminated Candida albicans infection and implications for antifungal immunotherapyAlieke G Vonk
Radboud University Nijmegen Medical Center, Department of Medicine 463, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Expert Opin Biol Ther 6:891-903. 2006..Here, the authors review the chronological events in the pathogenesis of disseminated candidiasis that aid in predicting the impact of existing immunotherapy and the development of future immunomodulating strategies...
Crohn's disease patients homozygous for the 3020insC NOD2 mutation have a defective NOD2/TLR4 cross-tolerance to intestinal stimuliBart Jan Kullberg
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, and Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands
Immunology 123:600-5. 2008..In conclusion, we propose the absence of NOD2/TLR4 cross-tolerance as a central mechanism for the increased susceptibility to Crohn's disease in individuals with NOD2 mutations...
Role of TLR1 and TLR6 in the host defense against disseminated candidiasisMihai G Netea
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
FEMS Immunol Med Microbiol 52:118-23. 2008..In conclusion, TLR6 is involved in the recognition of C. albicans and modulates the Th1/Th2 cytokine balance, but this results in a mild phenotype with a normal susceptibility of TLR6-/- mice to Candida infection...
An integrated model of the recognition of Candida albicans by the innate immune systemMihai G Netea
Department of Medicine and Nijmegen University Centre for Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Nat Rev Microbiol 6:67-78. 2008..In this Review, we use the fungal pathogen Candida albicans as a model for the complex interaction that exists between the host pattern-recognition systems and invading microbial pathogens...
Phagocytosis and intracellular killing of Candida albicans blastoconidia by neutrophils and macrophages: a comparison of different microbiological test systemsAlieke G Vonk
Department of Medicine (541, Division of General Internal Medicine, Nijmegen University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
J Microbiol Methods 49:55-62. 2002....
Does the shape of lipid A determine the interaction of LPS with Toll-like receptors?Mihai G Netea
Dept of Medicine, Division of General Internal Medicine, University Medical Center St Radboud, Geert Grooteplein 8, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
Trends Immunol 23:135-9. 2002..Strictly cylindrical LPS molecules (e.g. the lipid A precursor Ia or from Rhodobacter sphaeroides) have antagonistic properties at the level of TLRs...
Non-LPS components of Chlamydia pneumoniae stimulate cytokine production through Toll-like receptor 2-dependent pathwaysMihai G Netea
Department of Medicine, University Medical Center St Radboud, Nijmegen, The Netherlands
Eur J Immunol 32:1188-95. 2002..pneumoniae stimulates cytokine production in a serum-dependent manner, but independently of complement, MBL and LBP. C. pneumoniae induces the pro-inflammatory cytokines TNF and IL-1beta through TLR2, but not TLR4 and CD14...
Divergent effects of tumor necrosis factor-alpha and lymphotoxin-alpha on lethal endotoxemia and infection with live Salmonella typhimurium in miceEdi Dharmana
Department of Parasitology, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
Eur Cytokine Netw 13:104-9. 2002..typhimurium LPS and on the infection of mice with live Salmonella microorganisms, and suggest caution when extrapolating results obtained in the lethal endotoxemia model to bacteremia in patients...
Redundant role of TLR9 for anti-Candida host defenseFrank Leo van de Veerdonk
Immunobiology 213:613-20. 2008..albicans. However, the cytokine defect in TLR9-/- mice is compensated by alternative pathways, and the TLR9-dependent pathway seems to be redundant in the disseminated candidiasis model in mice...
CD40/CD40 ligand interactions in the host defense against disseminated Candida albicans infection: the role of macrophage-derived nitric oxideMihai G Netea
Department of Medicine, University Medical Center St Radboud, Nijmegen, The Netherlands
Eur J Immunol 32:1455-63. 2002..In conclusion, absence of CD40/CD40L interactions results in increased susceptibility to disseminated infection with C. albicans through decreased NO-dependent killing of Candida by macrophages...
Mycobacterium paratuberculosis is recognized by Toll-like receptors and NOD2Gerben Ferwerda
Department of Internal Medicine and Nijmegen University Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
J Leukoc Biol 82:1011-8. 2007..paratuberculosis. These results demonstrate that TLR2, TLR4, and NOD2 are involved in the recognition of M. paratuberculosis by the innate immune system...
The role of toll-like receptor (TLR) 2 and TLR4 in the host defense against disseminated candidiasisMihai G Netea
Department of Medicine, Division of General Internal Medicine, University Medical Center St Radboud, Nijmegen, The Netherlands
J Infect Dis 185:1483-9. 2002..In conclusion, TLR4-defective C3H/HeJ mice are more susceptible to C. albicans infection, and this is associated with impaired chemokine expression and neutrophil recruitment...
Role of interleukin-18 in host defense against disseminated Candida albicans infectionRogier J L Stuyt
Department of Medicine, University Medical Center St. Radboud, Nijmegen, The Netherlands
Infect Immun 70:3284-6. 2002..There was no effect on the organ load with Candida when gamma interferon (IFN-gamma)-deficient mice were treated with anti-IL-18 antibodies, suggesting that the protective effect of IL-18 is mediated through endogenous IFN-gamma...
Sepsis--theory and therapiesMihai G Netea
N Engl J Med 348:1600-2; author reply 1600-2. 2003
Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistanceMihai G Netea
Department of Internal Medicine and Nijmegen University Center for Infectious Diseases, Geert Grooteplein 8, 6500 HB, Nijmegen, The Netherlands
Nat Med 12:650-6. 2006..In addition, rIL-18 reversed hyperglycemia in Il18-/- mice through activation of STAT3 phosphorylation. These findings indicate a new role of IL-18 in the homeostasis of energy intake and insulin sensitivity...
Treatment of intra-abdominal abscesses caused by Candida albicans with antifungal agents and recombinant murine granulocyte colony-stimulating factorAlieke G Vonk
Department of Medicine, Division of General Internal Medicine. Department of Pathology, University Medical Center Nijmegen, The Netherlands
Antimicrob Agents Chemother 47:3688-93. 2003..In contrast, addition of rmG-CSF therapy to antifungal treatment might further enhance the beneficial effect of the antifungal agent...
Effect of recombinant murine granulocyte colony-stimulating factor with or without fluoroquinolone therapy on mixed-infection abscesses in miceLorna E T Stearne
Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
Antimicrob Agents Chemother 49:3668-75. 2005..In conclusion, the addition of G-CSF to a fluoroquinolone is not advisable since, depending on the virulence of the E. coli strains, this might detrimentally influence the outcome of therapy...
Interleukin-18 does not modulate the acute-phase responseRogier J L Stuyt
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
J Endotoxin Res 11:85-8. 2005..In conclusion, rIL-18 is not able to induce a febrile response in rabbits and does not modulate the acute-phase response in mice...
Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphismChantal van der Graaf
Department of Medicine, University Medical Center St Radboud Nijmegen, The Netherlands
Cytokine 30:264-8. 2005..In addition, this is the first study to demonstrate that even homozygosity for the Asp299Gly mutation does not confer hyporesponsiveness to stimulation with TLR4 stimuli...
Nucleotide-binding oligomerization domain-2 modulates specific TLR pathways for the induction of cytokine releaseMihai G Netea
Department of Medicine, Radboud University Medical Center Nijmegen, The Netherlands
J Immunol 174:6518-23. 2005..Thus, interaction between NOD2 and specific TLR pathways may represent an important modulatory mechanism of innate immune responses...
Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cellsMihai G Netea
Department of Medicine, University Medical Center St Radboud, Nijmegen, The Netherlands
J Immunol 172:3712-8. 2004..In conclusion, C. albicans induces immunosuppression through TLR2-derived signals that mediate increased IL-10 production and survival of Treg cells. This represents a novel mechanism in the pathogenesis of fungal infections...
Apolipoprotein-E-deficient mice exhibit an increased susceptibility to disseminated candidiasisAlieke G Vonk
Division of General Internal Medicine, Department of Medicine, University Medical Center, Nijmegen, The Netherlands
Med Mycol 42:341-8. 2004..This study suggests that lipoproteins play a significant role in host defense against candidiasis...
Recombinant interleukin-18 protects against disseminated Candida albicans infection in miceRogier J L Stuyt
Department of Medicine, University Medical Center St. Radboud, Nijmegen, The Netherlands
J Infect Dis 189:1524-7. 2004..albicans in rIL-18-treated mice. In conclusion, rIL-18 improves outcome of disseminated candidiasis in mice and may prove useful as adjuvant immunotherapy of fungal infections...
Human dendritic cells are less potent at killing Candida albicans than both monocytes and macrophagesMihai G Netea
Department of Medicine, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
Microbes Infect 6:985-9. 2004..albicans hyphae. Effective handling of large numbers of C. albicans is the prime task of the innate immune system consisting of large numbers of neutrophils and monocytes...
Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune systemMihai G Netea
Department of Medicine, University Medical Center St Radboud, Nijmegen University, The Netherlands
J Leukoc Biol 75:749-55. 2004..Finally, the crucial role of TLRs for the host defense against infections has been strengthened recently by the description of patients partially defective in the TLR-activation pathways...
Chlamydia pneumoniae stimulates IFN-gamma synthesis through MyD88-dependent, TLR2- and TLR4-independent induction of IL-18 releaseMihai G Netea
Department of Medicine, University Medical Center Nijmegen, The Netherlands
J Immunol 173:1477-82. 2004..Most interestingly, C. pneumoniae is also a potent inducer of IL-18 production through pathways independent of TLR2 and TLR4...
NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's diseaseMihai G Netea
Department of Medicine, University Medical Center St Radboud, Nijmegen, The Netherlands
Eur J Immunol 34:2052-9. 2004..In conclusion, defective NOD2 function results in a pro-inflammatory cytokine bias after stimulation of mononuclear cells with TLR2 stimuli, and this could contribute to the overwhelming inflammation seen in Crohn's disease...
Differential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infectionMihai G Netea
Department of Medicine, University Medical Center St. Radboud, Nijmegen, Nijmegen, The Netherlands
Eur J Immunol 33:3409-17. 2003..In conclusion, the anticandidal effects of endogenous IL-18 are mediated late during the infection by assuring a proper IFN-gamma response and promoting the infiltration of the site of infection by monocytes...
Differential cytokine production and Toll-like receptor signaling pathways by Candida albicans blastoconidia and hyphaeChantal A A Van der Graaf
Department of Medicine 541, Radboud University Nijmegen Medical Center, P O Box 9101, 6500 HB Nijmegen, The Netherlands
Infect Immun 73:7458-64. 2005..TLR4-mediated proinflammatory signals are lost during germination of Candida blastoconidia into hyphae. Phenotypic switching during germination may be an important escape mechanism of C. albicans, resulting in counteracting host defense...
Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptorsMihai G Netea
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
J Clin Invest 116:1642-50. 2006..We concluded that recognition of C. albicans by monocytes/macrophages is mediated by 3 recognition systems of differing importance, each of which senses specific layers of the C. albicans cell wall...
Proinflammatory cytokines and sepsis syndrome: not enough, or too much of a good thing?Mihai G Netea
Department of Medicine (541, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Trends Immunol 24:254-8. 2003
The role of endogenous interleukin (IL)-18, IL-12, IL-1beta, and tumor necrosis factor-alpha in the production of interferon-gamma induced by Candida albicans in human whole-blood culturesMihai G Netea
Department of Medicine and Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, USA
J Infect Dis 185:963-70. 2002..Blocking the biologic activities of IL-18, IL-12, and IL-1beta in patients (e.g., for treatment of autoimmune diseases) may result in increased susceptibility to C. albicans infection...
Endogenous interleukin (IL)-1 alpha and IL-1 beta are crucial for host defense against disseminated candidiasisAlieke G Vonk
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
J Infect Dis 193:1419-26. 2006..It is, however, unknown whether they provide protection through similar mechanisms. We investigated the effect of endogenous IL-1 alpha and IL-1 beta on disseminated C. albicans infection...
Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infectionChantal A A Van der Graaf
Department of Internal Medicine 463, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Eur Cytokine Netw 17:29-34. 2006..These findings show that the TLR4 Asp299Gly/Thr399Ile polymorphisms are associated with an increased susceptibility to Candida bloodstream infections, and an increased production of IL-10 is probably involved in this effect...
Nucleotide oligomerization domain 2 (Nod2) is not involved in the pattern recognition of Candida albicansChantal A A Van der Graaf
Department of Medicine, Radboud University Nijmegen Medical Center, P O Box 9101, 6500 HB Nijmegen, The Netherlands
Clin Vaccine Immunol 13:423-5. 2006..Candida-induced cytokine production in individuals with Nod2 polymorphisms was unaffected. We conclude that Nod2 is unlikely to play an important role in the recognition of Candida albicans...
Impaired dendritic cell function in Crohn's disease patients with NOD2 3020insC mutationMatthijs Kramer
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, 6525 GA, Nijmegen, The Netherlands
J Leukoc Biol 79:860-6. 2006..These data indicate that the NOD2fs mutation results in a loss-of-function phenotype in human myeloid DC and imply decreased immune regulation by IL-10 as a possible mechanism for this mutation in CD...
Selective regulation of intercellular adhesion molecule-1 expression by interleukin-18 and interleukin-12 on human monocytesRogier J L Stuyt
Department of Medicine, University Medical Center St. Radboud, Nijmegen, The Netherlands
Immunology 110:329-34. 2003..In conclusion, IL-18 selectively up-regulates the expression of ICAM-1 on monocytes, and this contributes to the proinflammatory effects of this cytokine...
Influence of endogenous pro-inflammatory cytokines on neutrophil-mediated damage of Candida albicans pseudohyphae, quantified in a modified tetrazolium dye assayAlieke G Vonk
Department of Medicine, Division of General Internal Medicine, Radboud University Nijmegen Medical Center, The Netherlands
Med Mycol 43:551-7. 2005....
Salmonella septicemia in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: association with decreased interferon-gamma production and Toll-like receptor 4 expressionMihai G Netea
University Medical Center St. Radboud, and Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands
Arthritis Rheum 48:1853-7. 2003....
Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transductionMihai G Netea
Department of Medicine 541, University Medical Center St Radboud, 6500 HB Nijmegen, The Netherlands
J Infect Dis 188:320-6. 2003..Therefore, phenotypic switching during germination may be an important escape mechanism of A. fumigatus that results in counteracting the host defense...
Detection of the Candida antigen mannan in cerebrospinal fluid specimens from patients suspected of having Candida meningitisFrans M Verduyn Lunel
Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands
J Clin Microbiol 42:867-70. 2004..Samples from the remaining patient and from patients with other central nervous system infections were negative. Detection of mannan may be valuable in the diagnosis of Candida meningitis...
Drosomycin-like defensin, a human homologue of Drosophila melanogaster drosomycin with antifungal activityAnna Simon
Department of Medicine 463, Radboud University Nijmegen Medical Center, Geert Grooteplein 8, 6500 HB, Nijmegen, The Netherlands
Antimicrob Agents Chemother 52:1407-12. 2008..This is the first indication of an endogenous human peptide with specific antifungal activity, which is probably central in the defense against infections with molds...
Host-microbe interactions: innate pattern recognition of fungal pathogensFrank L van de Veerdonk
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Curr Opin Microbiol 11:305-12. 2008..This will determine a divergence of the final type of reaction, and in this way the innate host defense has the capability to deliver tailored responses to each pathogen...
Two patients with cryptococcal meningitis and idiopathic CD4 lymphopenia: defective cytokine production and reversal by recombinant interferon- gamma therapyMihai G Netea
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands
Clin Infect Dis 39:e83-7. 2004..CONCLUSIONS: Refractory meningitis may be due to defective TNF and IFN- gamma production, and IFN- gamma treatment may be useful in patients with an impaired cellular immune response and refractory cryptococcal meningitis...
