64 results on '"Vonk, Alieke G"'
Search Results
52. Validation of a New AspergillusReal-Time PCR Assay for Direct Detection of Aspergillusand Azole Resistance of Aspergillus fumigatuson Bronchoalveolar Lavage Fluid
- Author
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Chong, Ga-Lai M., van de Sande, Wendy W. J., Dingemans, Gijs J. H., Gaajetaan, Giel R., Vonk, Alieke G., Hayette, Marie-Pierre, van Tegelen, Dennis W. E., Simons, Guus F. M., and Rijnders, Bart J. A.
- Abstract
ABSTRACTAzole resistance in Aspergillus fumigatusis increasingly reported. Here, we describe the validation of the AsperGenius, a new multiplex real-time PCR assay consisting of two multiplex real-time PCRs, one that identifies the clinically relevant Aspergillusspecies, and one that detects the TR34, L98H, T289A, and Y121F mutations in CYP51A and differentiates susceptible from resistant A. fumigatusstrains. The diagnostic performance of the AsperGenius assay was tested on 37 bronchoalveolar lavage (BAL) fluid samples from hematology patients and 40 BAL fluid samples from intensive care unit (ICU) patients using a BAL fluid galactomannan level of =1.0 or positive culture as the gold standard for detecting the presence of Aspergillus. In the hematology and ICU groups combined, there were 22 BAL fluid samples from patients with invasive aspergillosis (IA) (2 proven, 9 probable, and 11 nonclassifiable). Nineteen of the 22 BAL fluid samples were positive, according to the gold standard. The optimal cycle threshold value for the presence of Aspergilluswas <36. Sixteen of the 19 BAL fluid samples had a positive PCR (2 Aspergillusspecies and 14 A. fumigatussamples). This resulted in a sensitivity, specificity, and positive and negative predictive values of 88.9%, 89.3%, 72.7%, and 96.2%, respectively, for the hematology group and 80.0%, 93.3%, 80.0%, and 93.3%, respectively, in the ICU group. The CYP51A real-time PCR confirmed 12 wild-type and 2 resistant strains (1 TR34-L98H and 1 TR46-Y121F-T289A mutant). Voriconazole therapy failed for both patients. The AsperGenius multiplex real-time PCR assay allows for sensitive and fast detection of Aspergillusspecies directly from BAL fluid samples. More importantly, this assay detects and differentiates wild-type from resistant strains, even if BAL fluid cultures remain negative.
- Published
- 2014
- Full Text
- View/download PDF
53. Influence of endogenous pro-inflammatory cytokines on neutrophil-mediated damage of Candida albicans pseudohyphae, quantified in a modified tetrazolium dye assay.
- Author
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Vonk, Alieke G., Wieland, Catharina W., Versteegen, Marieke, Verschueren, Ineke C., Netea, Mihai G., Joosten, Leo A. B., Verweij, Paul E., and Kullberg, Bart Jan
- Subjects
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GRANULOCYTES , *TETRAZOLIUM , *CANDIDA albicans , *INTERFERONS , *INTERLEUKIN-1 - Abstract
For quantitative assessment of polymorphonuclear granulocyte (PMN)-mediated pseudohyphal damage, an improved tetrazolium (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide; XTT) dye assay was developed. The modified assay proved to be a reliable indicator of viable pseudohyphal inoculum sizes. In addition, the influence of various endogenous pro-inflammatory cytokines on the capacity of PMN to damage Candida albicans pseudohyphae was investigated. PMN obtained from mice in which the genes encoding for tumor necrosis factor-α /lymphotoxin-α (TNF/LT), interferon-γ (IFNγ), interleukin (IL)-1α, or IL-1β were disrupted, showed a significantly reduced pseudohyphal damage capacity in comparison with control PMN. The reduction amounted 25% for TNF -/ - LT -/ - , 11% for IFNγ -/ - , 21% for IL-1α -/ - , and 34% for IL-1α -/ - β -/ - PMN. In contrast, deficiency of IL-12 or IL-18 did not result in a diminished capacity to damage pseudohyphae and the capacity of PMN to damage Candida pseudohyphae was even slightly increased by 10% in IL-18 -/ - mice. These data suggest that endogenous pro-inflammatory cytokines are able to modulate antihyphal activity of PMN, the main effector cells against disseminated candidiasis by virtue of their capacity to kill both Candida blastoconidia and pseudohyphae. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
54. Differential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infection.
- Author
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Netea, Mihai G., Vonk, Alieke G., van den Hoven, Mabel, Verschueren, Ineke, Joosten, Leo A., van Krieken, Johan H., van den Berg, Wim B., Van der Meer, Jos W. M., and Kullberg, Bart Jan
- Abstract
IFN-γ plays a crucial role in the defense against infection with Candida albicans. Since IL-18 and IL-12 are strong stimuli of IFN-γ production, we investigated whether endogenous IL-18 and IL-12 are involved in the host defense during disseminated candidiasis. IL-18 knockout (IL-18-/-) mice, but not IL-12-/- mice, displayed an increased mortality due to C. albicans infection, accompanied by a decreased clearance of the yeasts from the kidneys late during the course of infection. Histopathology of the organs, combined with phagocyte recruitment experiments, showed a decreased influx of monocytes at the sites of Candida infection, mainly in the IL-18-/- mice. Whereas production of the chemokine KC was decreased in both IL-18-/- and IL-12-/- mice, MIP-2 production was deficient only in IL-18-/- animals, which may explain the differences in phagocyte recruitment. In addition, although IFN-γ production capacity, as a parameter of the Th1-protective immunity, was reduced by 65 to 80% in the IL-12-/- mice, this defect was even more pronounced in the IL-18-/- mice (85 to 95% downmodulation). In conclusion, the anticandidal effects of endogenous IL-18 are mediated late during the infection by assuring a proper IFN-γ response and promoting the infiltration of the site of infection by monocytes. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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55. Delayed Clearance of Intraabdominal Abscesses Caused by Candida albicans in Tumor Necrosis Factor-α-and Lymphotoxin-α-Deficient Mice.
- Author
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Vonk, Alieke G., Netea, Mihai G., van Krieken, Johan H., van der Meer, Jos W.M., and Kullberg, Bart Jan
- Subjects
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TUMOR necrosis factors , *CANDIDA , *ABSCESSES - Abstract
The role of endogenous tumor necrosis factor-α (TNF) and lymphotoxin-α (LT) in a model of intraabdominal Candida sepsis and abscess formation was investigated. Significantly more abscesses were observed in TNF/LT double knockout (TNF[sup -/-]LT[sup -/-]) mice, compared with that in wild-type (TNF[sup +/+]LT[sup +/+]) mice. Outgrowth of Candida in abscesses of TNF[sup -/-]LT[sup -/-] mice was 10-fold increased on day 14 and 60-fold increased on day 21 of infection. The interleukin10:interferon-γ ratio, measured in supernatants of stimulated splenocytes, shifted from 131 for TNF[sup -/-]LT[sup -/-] mice and 13.9 for TNF[sup +/+]LT[sup +/+] mice on day 8 to 0.11 for TNF[sup -/-] LT[sup -/-] mice and 11.66 for TNF[sup +/+]LT[sup +/+] mice on day 14 of infection. The diminished host resistance is explained by an impaired extracellular killing capacity of granulocytes and a delayed development of a T helper 1 response in TNF[sup -/-]LT[sup -/-] mice. In conclusion, TNF and LT are critical to the stimulation of effector cells that leads to elimination of Candida from abscesses. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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56. Modulation of neutrophil function in host defense against disseminated Candida albicans infection in mice.
- Author
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Kullberg, Bart Jan, Netea, Mihai G, Vonk, Alieke G, and Meer, Jos W.M
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- 1999
- Full Text
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57. Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses by Aspergillus fumigatus
- Author
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Chai, Louis Y. A., Kullberg, Bart Jan, Vonk, Alieke G., Warris, Adilia, Cambi, Alessandra, Latgé, Jean-Paul, Joosten, Leo A. B., van der Meer, Jos W. M., and Netea, Mihai G.
- Abstract
Toll-like receptor (TLR)-based signaling pathways in the host may be modulated by pathogens during the course of infection. We describe a novel immunomodulatory mechanism in which Aspergillus fumigatus conidia induce attenuation of TLR2- and TLR4-mediated interleukin (IL)-6 and IL-1β proinflammatory responses in human mononuclear cells with suppression of IL-1β mRNA transcription. Background TLR2 and TLR4 mRNA transcription was not influenced. A. fumigatus conidia induced TLR2 internalization and uptake into the phagosome with a resultant decrease in surface receptor expression. A. fumigatus hyphae, on the other hand, selectively downregulated the TLR4-mediated response. These novel immunosuppressive effects may facilitate the invasiveness of A. fumigatus.
- Published
- 2009
58. Host defence against disseminated Candida albicansinfection and implications for antifungal immunotherapy
- Author
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Vonk, Alieke G, Netea, Mihai G, van der Meer, Jos WM, and Kullberg, Bart Jan
- Abstract
The different manifestations of Candida albicansinfection are dictated by an underlying defect in the immune response of the host. Protective immunity to disseminated candidiasis, the manifestation of C. albicansinfection discussed in this review, has traditionally been ascribed to innate immunity with emphasis on the role of granulocytes. Lately, however, immunological studies have learned that host defence against disseminated candidiasis is based on a complex interplay between innate and cell-mediated immunity. Despite the availability of new antifungal agents, mortality associated with disseminated C. albicansinfection remains high. Immunotherapy that augments host defence is an important strategic option in the battle against disseminated candidiasis. 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.
- Published
- 2006
- Full Text
- View/download PDF
59. Treatment of Intra-Abdominal Abscesses Caused by Candida albicanswith Antifungal Agents and Recombinant Murine Granulocyte Colony-Stimulating Factor
- Author
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Vonk, Alieke G., Netea, Mihai G., van Krieken, Johan H., Verweij, Paul E., van der Meer, Jos W. M., and Kullberg, Bart Jan
- Abstract
ABSTRACTThe aim of the present study was to assess the influence of immunomodulation of host defense with recombinant murine granulocyte colony-stimulating factor (rmG-CSF) on intra-abdominal abscesses caused by Candida albicans. Mice received prophylaxis or therapy with 1 μg of rmG-CSF/day in the presence or absence of antifungal treatment consisting of amphotericin B (0.75 mg/kg of body weight/day) or fluconazole (50 mg/kg/day). The number of CandidaCFU in abscesses was significantly reduced (P< 0.05) in mice receiving rmG-CSF prophylaxis (day −1 or day −1 through 2) compared with controls on day 8 of infection. Administration of rmG-CSF therapy alone (for 5 days starting on day 4 of infection) had no influence on the number of CandidaCFU in abscesses. Amphotericin B treatment was significantly more effective than fluconazole treatment (3.41 log CFU/abscesses; 95% confidence interval [CI], 3.17 log CFU/abscesses; 3.65 versus 3.90 log CFU/abscesses; 95% CI, 3.66 log CFU/abscesses, 4.16 log CFU/abscesses; P< 0.05). Therapeutic administration of rmG-CSF in conjunction with an antifungal agent showed a tendency towards a further reduction of CandidaCFU in abscesses than antifungal treatment only. In conclusion, in this experimental model of intra-abdominal Candidaabscesses, rmG-CSF administration did not have a detrimental influence on the course of infection. Amphotericin B treatment was most effective, and additional rmG-CSF therapy did not antagonize the effect of antifungal treatment. In contrast, addition of rmG-CSF therapy to antifungal treatment might further enhance the beneficial effect of the antifungal agent.
- Published
- 2003
- Full Text
- View/download PDF
60. Modulation of neutrophil function in host defense against disseminated Candida albicansinfection in mice
- Author
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Kullberg, Bart Jan, Netea, Mihai G, Vonk, Alieke G, and Meer, Jos W.M
- Abstract
Neutrophils (PMNs) constitute the main mechanism of host defense against acute invasive and disseminated candidiasis. Recent studies have demonstrated that tumor necrosis factor‐α (TNFα), interleukin‐6 (IL‐6) and granulocyte colony‐stimulating factor (G‐CSF) play an important role in the recruitment of PMNs at the site of invasive Candidainfection. In the absence of either TNFα or IL‐6, the course of experimental disseminated candidiasis is more severe, due to defective PMN recruitment. Treatment of mice with recombinant G‐CSF (rG‐CSF) leads to a significantly reduced mortality during disseminated candidiasis. The outgrowth of Candida albicansfrom the organs of rG‐CSF‐treated mice is significantly decreased. Treatment with the combination of rG‐CSF and fluconazole has an additive effect on the reduction of fungal load in the organs. In subacute or chronic disseminated Candidainfection, rG‐CSF is less effective, indicating that neutrophil recruitment and activation are crucial in acute, life‐threatening candidiasis, whereas other host defense mechanisms control the outcome of less overwhelming invasive Candidainfection.
- Published
- 1999
- Full Text
- View/download PDF
61. Chitinase Induction Prior to Caspofungin Treatment of Experimental Invasive Aspergillosis in Neutropenic Rats Does Not Enhance Survival
- Author
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Refos, Jeannine M., Vonk, Alieke G., ten Kate, Marian T., Verbrugh, Henri A., Bakker-Woudenberg, Irma A. J. M., and van de Sande, Wendy W. J.
- Abstract
ABSTRACTHost chitinases, chitotriosidase and acidic mammalian chitinase (AMCase), improved the antifungal activity of caspofungin (CAS) against Aspergillus fumigatus in vitro. These chitinases are not constitutively expressed in the lung. Here, we investigated whether chitosan derivatives were able to induce chitinase activity in the lungs of neutropenic rats and, if so, whether these chitinases were able to prolong survival of rats with invasive pulmonary aspergillosis (IPA) or of rats with IPA and treated with CAS. An oligosaccharide-lactate chitosan (OLC) derivative was instilled in the left lung of neutropenic rats to induce chitotriosidase and AMCase activities. Rats instilled with OLC or with phosphate-buffered saline (PBS) were subsequently infected with A. fumigatusand then treated with suboptimal doses of CAS. Survival, histopathology, and galactomannan indexes were determined. Instillation of OLC resulted in chitotriosidase and AMCase activities. However, instillation of OLC did not prolong rat survival when rats were subsequently challenged with A. fumigatus. In 5 of 7 rats instilled with OLC, the fungal foci in the lungs were smaller than those in rats instilled with PBS. Instillation of OLC did not significantly enhance the survival of neutropenic rats challenged with A. fumigatusand treated with a suboptimal dosage of CAS. Chitotriosidase and AMCase activities can be induced with OLC, but the presence of active chitinases in the lung did not prevent the development of IPA or significantly enhance the therapeutic outcome of CAS treatment.
- Published
- 2017
- Full Text
- View/download PDF
62. Periocular tinea caused by zoonotic Trichophyton benhamiae.
- Author
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Sips GJ, Lekkerkerk WSN, Boddé E, Broens EM, Vonk AG, and Thio HB
- Subjects
- Animals, Bacterial Zoonoses, Female, Humans, Middle Aged, Tinea etiology, Antifungal Agents therapeutic use, Arthrodermataceae isolation & purification, Terbinafine therapeutic use, Tinea microbiology
- Abstract
Competing Interests: Declaration of interests We declare no competing interests.
- Published
- 2021
- Full Text
- View/download PDF
63. Host defence against disseminated Candida albicans infection and implications for antifungal immunotherapy.
- Author
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Vonk AG, Netea MG, van der Meer JW, and Kullberg BJ
- Subjects
- Adjuvants, Immunologic economics, Animals, Candidiasis immunology, Candidiasis prevention & control, Complement System Proteins immunology, Dendritic Cells immunology, Drug Therapy, Combination, Fluconazole therapeutic use, Fungal Vaccines administration & dosage, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Immunity, Cellular drug effects, Immunity, Innate drug effects, Interferon-gamma therapeutic use, Killer Cells, Natural immunology, Phagocytes immunology, Randomized Controlled Trials as Topic economics, Receptors, Pattern Recognition immunology, Recombinant Proteins, Th1 Cells immunology, Th2 Cells immunology, Adjuvants, Immunologic therapeutic use, Antifungal Agents therapeutic use, Candida albicans immunology, Candidiasis drug therapy
- Abstract
The different manifestations of Candida albicans infection are dictated by an underlying defect in the immune response of the host. Protective immunity to disseminated candidiasis, the manifestation of C. albicans infection discussed in this review, has traditionally been ascribed to innate immunity with emphasis on the role of granulocytes. Lately, however, immunological studies have learned that host defence against disseminated candidiasis is based on a complex interplay between innate and cell-mediated immunity. Despite the availability of new antifungal agents, mortality associated with disseminated C. albicans infection remains high. Immunotherapy that augments host defence is an important strategic option in the battle against disseminated candidiasis. 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.
- Published
- 2006
- Full Text
- View/download PDF
64. Treatment of intra-abdominal abscesses caused by Candida albicans with antifungal agents and recombinant murine granulocyte colony-stimulating factor.
- Author
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Vonk AG, Netea MG, van Krieken JH, Verweij PE, van der Meer JW, and Kullberg BJ
- Subjects
- Adjuvants, Immunologic pharmacokinetics, Adjuvants, Immunologic therapeutic use, Amphotericin B pharmacokinetics, Amphotericin B therapeutic use, Animals, Antifungal Agents pharmacokinetics, Cytokines biosynthesis, Female, Fluconazole therapeutic use, Granulocyte Colony-Stimulating Factor pharmacokinetics, Lymphocytes drug effects, Lymphocytes immunology, Mice, Mice, Inbred CBA, Microbial Sensitivity Tests, Recombinant Proteins pharmacokinetics, Recombinant Proteins therapeutic use, Spleen cytology, Spleen drug effects, Treatment Outcome, Abdominal Abscess drug therapy, Abdominal Abscess microbiology, Antifungal Agents therapeutic use, Candida albicans drug effects, Granulocyte Colony-Stimulating Factor therapeutic use
- Abstract
The aim of the present study was to assess the influence of immunomodulation of host defense with recombinant murine granulocyte colony-stimulating factor (rmG-CSF) on intra-abdominal abscesses caused by Candida albicans. Mice received prophylaxis or therapy with 1 microg of rmG-CSF/day in the presence or absence of antifungal treatment consisting of amphotericin B (0.75 mg/kg of body weight/day) or fluconazole (50 mg/kg/day). The number of Candida CFU in abscesses was significantly reduced (P<0.05) in mice receiving rmG-CSF prophylaxis (day -1 or day -1 through 2) compared with controls on day 8 of infection. Administration of rmG-CSF therapy alone (for 5 days starting on day 4 of infection) had no influence on the number of Candida CFU in abscesses. Amphotericin B treatment was significantly more effective than fluconazole treatment (3.41 log CFU/abscesses; 95% confidence interval [CI], 3.17 log CFU/abscesses; 3.65 versus 3.90 log CFU/abscesses; 95% CI, 3.66 log CFU/abscesses, 4.16 log CFU/abscesses; P<0.05). Therapeutic administration of rmG-CSF in conjunction with an antifungal agent showed a tendency towards a further reduction of Candida CFU in abscesses than antifungal treatment only. In conclusion, in this experimental model of intra-abdominal Candida abscesses, rmG-CSF administration did not have a detrimental influence on the course of infection. Amphotericin B treatment was most effective, and additional rmG-CSF therapy did not antagonize the effect of antifungal treatment. In contrast, addition of rmG-CSF therapy to antifungal treatment might further enhance the beneficial effect of the antifungal agent.
- Published
- 2003
- Full Text
- View/download PDF
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