43 results on '"Vonk, Alieke G"'
Search Results
2. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study
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Schauwvlieghe, Alexander F A D, Rijnders, Bart J A, Philips, Nele, Verwijs, Rosanne, Vanderbeke, Lore, Van Tienen, Carla, Lagrou, Katrien, Verweij, Paul E, Van de Veerdonk, Frank L, Gommers, Diederik, Spronk, Peter, Bergmans, Dennis C J J, Hoedemaekers, Astrid, Andrinopoulou, Eleni-Rosalina, van den Berg, Charlotte H S B, Juffermans, Nicole P, Hodiamont, Casper J, Vonk, Alieke G, Depuydt, Pieter, Boelens, Jerina, and Wauters, Joost
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- 2018
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3. The Y238X Stop Codon Polymorphism in the Human β-Glucan Receptor Dectin-1 and Susceptibility to Invasive Aspergillosis
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Chai, Louis Y.A., de Boer, Mark G. J., van der Velden, Walter J. F. M., Plantinga, Theo S., van Spriel, Annemiek B., Jacobs, Cor, Halkes, Constantijn J. M., Vonk, Alieke G., Blijlevens, Nicole M., van Dissel, Jaap T., Donnelly, Peter J., Kullberg, Bart-Jan, Maertens, Johan, and Netea, Mihai G.
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- 2011
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4. Early Proinflammatory Cytokines and C-Reactive Protein Trends as Predictors of Outcome in Invasive Aspergillosis
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Chai, Louis Y. A., Netea, Mihai G., Teerenstra, Steven, Earnest, Arul, Vonk, Alieke G., Schlamm, Haran T., Herbrecht, Raoul, Troke, Peter F., and Kullberg, Bart-Jan
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- 2010
5. Endogenous Interleukin (IL)-1α and IL-1β Are Crucial for Host Defense against Disseminated Candidiasis
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Vonk, Alieke G., Netea, Mihai G., van Krieken, Johan H., Iwakura, Yoichiro, van der Meer, Jos W. M., and Kullberg, Bart Jan
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- 2006
6. Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections
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van der Geest, Patrick J., Rijnders, Bart J. A., Vonk, Alieke G., and Groeneveld, Johan A. B.
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- 2016
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7. Aspergillus fumigatus Conidial Melanin Modulates Host Cytokine Response
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Chai, Louis Y.A., Netea, Mihai G., Sugui, Janyce, Vonk, Alieke G., van de Sande, Wendy W.J., Warris, Adilia, Kwon-Chung, Kyung J., and Jan Kullberg, Bart
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- 2010
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8. Delayed Clearance of Intraabdominal Abscesses Caused by Candida albicans in Tumor Necrosis Factor-α- and Lymphotoxin-a-Deficient Mice
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Vonk, Alieke G., Netea, Mihai G., van Krieken, Johan H., van der Meer, Jos W. M., and Kullberg, Bart Jan
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- 2002
9. The Role of Toll-like Receptor (TLR) 2 and TLR4 in the Host Defense against Disseminated Candidiasis
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Netea, Mihai G., Van der Graaf, Chantal A. A., Vonk, Alieke G., Verschueren, Ineke, Van der Meer, Jos W. M., and Kullberg, Bart Jan
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- 2002
10. Modulation of the Pro- and Antiinflammatory Cytokines by Amphotericin B [with Reply]
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Vonk, Alieke G., Netea, Mihai G., van der Meer, Jos W. M., Kullberg, Bart Jan, Rogers, P. David, Jenkins, John K., Chapman, Stanley W., and Cleary, John D.
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- 1999
11. An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity
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Chai, Louis Y. A., Netea, Mihai G., Tai, Bee Choo, Khin, Lay Wai, Vonk, Alieke G., Teo, Boon Wee, Schlamm, Haran T., Herbrecht, Raoul, Donnelly, J. Peter, Troke, Peter F., and Kullberg, Bart-Jan
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- 2013
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12. Immune response to Aspergillus fumigatus in compromised hosts: from bedside to bench
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Chai, Louis YA, Vonk, Alieke G, Kullberg, Bart-Jan, and Netea, Mihai G
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- 2011
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13. Differential susceptibility to lethal endotoxaemia in mice deficient in IL-1α, IL-1β or IL-1 receptor type I
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JOOSTEN, LEO A.B., VAN DE VEERDONK, FRANK L., VONK, ALIEKE G., BOERMAN, OTTO C., KEUTER, MONIQUE, FANTUZZI, GIAMILLA, VERSCHUEREN, INEKE, VAN DER POLL, TOM, DINARELLO, CHARLES A., KULLBERG, BART JAN, VAN DER MEER, JOS W.M., and NETEA, MIHAI G.
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- 2010
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14. Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity
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Chai, Louis Y. A., van de Veerdonk, Frank, Marijnissen, Renoud J., Cheng, Shih-Chin, Khoo, Ai Leng, Hectors, Magda, Lagrou, Katrien, Vonk, Alieke G., Maertens, Johan, Joosten, Leo A. B., Kullberg, Bart-Jan, and Netea, Mihai G.
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- 2010
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15. Periocular tinea caused by zoonotic Trichophyton benhamiae
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Sips, Gregorius J, Lekkerkerk, Wouter S N, Boddé, Elisabeth, Broens, Els M, Vonk, Alieke G, and Thio, Hok Bing
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- 2021
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16. Lateral flow assays for diagnosing invasive pulmonary aspergillosis in adult hematology patients: A comparative multicenter study.
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Mercier, Toine, Dunbar, Albert, Kort, Elizabeth de, Schauwvlieghe, Alexander, Reynders, Marijke, Guldentops, Ellen, Blijlevens, Nicole M A, Vonk, Alieke G, Rijnders, Bart, Verweij, Paul E, Lagrou, Katrien, and Maertens, Johan
- Abstract
Fast diagnosis of invasive pulmonary aspergillosis (IPA) is essential as early adequate therapy improves survival. However, current microbiological methods suffer from a low sensitivity or a long turnaround time, often as a result of batching. Recently, two lateral flow assays for diagnosing IPA have been CE (Conformité Européenne)-marked and commercialized. These assays can be used for fast single sample testing. However, clinical validation and comparative studies are lacking. We therefore sought to evaluate and compare these assays in adult hematology patients. We retrospectively tested 235 bronchoalveolar lavage fluid (BALf) samples of adult hematology patients from four centers using the AspLFD (OLM Diagnostics) and the sōna Aspergillus galactomannan LFA (IMMY). Both tests were read out independently by two researchers and by a digital reader. We included 11 patients with proven IPA, 64 with probable IPA, 43 with possible fungal disease, and 117 controls with no signs of IPA. In cases of proven IPA, the performance of both assays was similar. In cases of proven and probable IPA, we found an identical specificity for both assays, but a higher sensitivity (0.83 vs 0.69, P =.008) and a better negative predictive value (0.89 vs 0.82, P =.009) for the LFA. Digital readout improved the diagnostic performance of both tests. In conclusion, both assays showed a good performance for the diagnosis of IPA in BALf from adult hematology patients. Results were further improved by using a digital reader, especially for weakly positive results. [ABSTRACT FROM AUTHOR]
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- 2020
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17. Mycovirus therapy for invasive pulmonary aspergillosis?
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Sande, Wendy W J van de and Vonk, Alieke G
- Abstract
With the current revived interest in the use of bacteriophages for the treatment of bacterial infections, the study of mycoviruses as novel therapeutic solutions for invasive aspergillosis is the logical next step. Although ssRNA, dsRNA, and ssDNA mycoviruses have been identified, the majority of characterised mycoviruses have dsRNA genomes. Prevalence of dsRNA mycoviruses in Aspergillus spp. varies, and mycoviruses can have different effects on their fungal hosts: hypovirulence, hypervirulence, or a killer phenotype. Therapeutically, extracellular transmission of the mycovirus is essential. DsRNA mycoviruses lack an extracellular phase; however, a single ssDNA mycovirus with homologues in Aspergillus genomes has been described with an extracellular mode of transmission. Mycoviruses can induce hypovirulence or a killer phenotype, and both can be exploited therapeutically. Mycoviruses inducing hypovirulence have been used to control chestnut blight, however for aspergillosis no such mycovirus has been identified yet. Mycovirus encoded killer toxins or anti-idiotypic antibodies and killer peptides derived from these have been demonstrated to control fungal infections including aspergillosis in animals. This indicates that mycoviruses inducing both phenotypes could be exploited therapeutically as long as the right mycovirus has been identified. [ABSTRACT FROM AUTHOR]
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- 2019
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18. The diagnosis and treatment of invasive aspergillosis in Dutch haematology units facing a rapidly increasing prevalence of azole‐resistance. A nationwide survey and rationale for the DB‐MSG 002 study protocol.
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Schauwvlieghe, Alexander F. A. D., De Jonge, Nick, Van Dijk, Karin, Verweij, Paul E., Brüggemann, Roger J., Biemond, Bart J., Bart, Aldert, Von Dem Borne, Peter A., Verbon, Annelies, Van Der Beek, Martha T., Demandt, Astrid M. P., Oudhuis, Guy J., Cornelissen, Jan J., Van Der Velden, Walter J. F. M., Span, Lambert F. R., Kampinga, Greetje A., Bruns, Anke H., Vonk, Alieke G., Haas, Pieter-jan A., and Doorduijn, Jeanette K.
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ASPERGILLOSIS diagnosis ,ASPERGILLOSIS treatment ,INTRODUCED fungi ,PHYSIOLOGICAL effects of azoles ,HEMATOLOGY - Abstract
Summary: Patients with haematological malignancies are at risk for invasive fungal diseases (IFD). A survey was conducted in all Dutch academic haematology centres on their current diagnostic, prophylactic and therapeutic approach towards IFD in the context of azole‐resistance. In all 8 centres, a haematologist and microbiologist filled in the questionnaire that focused on different subgroups of haematology patients. Fungal prophylaxis during neutropaenia was directed against Candida and consisted of fluconazole and/or amphotericin B suspension. Mould‐active prophylaxis was given to acute myeloid leukaemia patients during chemotherapy in 2 of 8 centres. All centres used azole prophylaxis in a subset of patients with graft‐versus‐host disease. A uniform approach towards the diagnosis and treatment of IFD and in particular azole‐resistant Aspergillus fumigatus was lacking. In 2017, all centres agreed to implement a uniform diagnostic and treatment algorithm regarding invasive aspergillosis with a central role for comprehensive diagnostics and PCR‐based detection of azole‐resistance. This study (DB‐MSG 002) will re‐evaluate this algorithm when 280 patients have been treated. A heterogeneous approach towards antifungal prophylaxis, diagnosis and treatment was apparent in the Netherlands. Facing triazole‐resistance, consensus was reached on the implementation of a uniform diagnostic approach in all 8 centres. [ABSTRACT FROM AUTHOR]
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- 2018
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19. Addition of 17-(allylamino)-17-demethoxygeldanamycin to a suboptimal caspofungin treatment regimen in neutropenic rats with invasive pulmonary aspergillosis delays the time to death but does not enhance the overall therapeutic efficacy.
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Refos, Jeannine M., Vonk, Alieke G., ten Kate, Marian T., Eadie, Kimberly, Verbrugh, Henri A., Bakker-Woudenberg, Irma A. J. M., and van de Sande, Wendy W. J.
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PULMONARY aspergillosis , *GELDANAMYCIN , *SALVAGE therapy , *AMINO acid derivatives , *ASPERGILLUS fumigatus , *LABORATORY rats , *THERAPEUTICS - Abstract
Caspofungin (CAS) which is used as salvage therapy in patients with invasive pulmonary aspergillosis (IPA) inhibits the 1,3-β-D-glucan synthesis in Aspergillus fumigatus. Inhibiting 1,3-β-D-glucan synthesis induces a stress response and in an invertebrate model it was demonstrated that inhibiting this response with geldamycin enhanced the therapeutic efficacy of CAS. Since geldamycin itself is toxic to mammalians, the therapeutic efficacy of combining geldamycin with CAS was not studied in rodent models. Therefore in this study we investigated if the geldamycin derivate 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) was able to enhance the therapeutic efficacy of CAS in vitro and in our IPA model in transiently neutropenic rats. In vitro we confirmed the earlier demonstrated synergy between 17-AAG and CAS in ten A. fumigatus isolates. In vivo we treated A. fumigatus infected neutropenic rats with a sub-optimal dose of 0.75 mg/kg/day CAS and 1 mg/kg/day 17-AAG for ten days. Survival was monitored for 21 days after fungal inoculation. It appeared that the addition 17-AAG delayed death but did not improve overall survival of rats with IPA. Increasing the doses of 17-AAG was not possible due to hepatic toxicity. This study underlines the need to develop less toxic and more fungal specific geldamycin derivatives and the need to test such drugs not only in invertebrate models but also in mammalian models. [ABSTRACT FROM AUTHOR]
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- 2017
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20. Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections.
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Geest, Patrick J., Rijnders, Bart J. A., Vonk, Alieke G., and Groeneveld, A. B. Johan
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ECHINOCANDINS ,INVASIVE candidiasis ,FLUCONAZOLE ,CANDIDA albicans ,INFECTION - Abstract
Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin. [ABSTRACT FROM AUTHOR]
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- 2016
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21. Voriconazole or Amphotericin B as Primary Therapy Yields Distinct Early Serum Galactomannan Trends Related to Outcomes in Invasive Aspergillosis.
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Chai, Louis Yi Ann, Kullberg, Bart Jan, Earnest, Arul, Johnson, Elizabeth M., Teerenstra, Steven, Vonk, Alieke G., Schlamm, Haran T., Herbrecht, Raoul, Netea, Mihai G., and Troke, Peter F.
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GALACTOMANNANS ,BLOOD serum analysis ,AMPHOTERICIN B ,ASPERGILLOSIS ,INTRODUCED fungi ,ANTIFUNGAL agents ,CLINICAL trials ,THERAPEUTICS - Abstract
An improved number of anti-fungal drugs are currently available for the treatment of invasive aspergillosis (IA). While serial galactomannan index (GMI) measurement can be used to monitor response to treatment, the extent to which different anti-fungal regimens can affect galactomannan levels is unknown. In 147 IA patients receiving either voriconazole (VCZ) or conventional amphotericin B (CAB) in a multicentre clinical trial, we performed post-hoc analyses of GMI trends in relation to outcomes. The generalized estimation equations approach was used to estimate changes in the effect size for GMI over time within patients. Patients who received VCZ primary therapy and had good treatment response 12 weeks later showed earlier decreases in GMI values at Week 1 and Week 2 (p = 0.001 and 0.046 respectively) as compared to patients who only received CAB. At end-of-randomized therapy (EORT), which was a pre-set secondary assessment point for all patients who switched from randomized primary (CAB or VCZ) to an alternative anti-fungal drug, treatment failure was associated with increasing GMI at Weeks 1 and 2 in CAB-primary treated patients (p = 0.022 and 0.046 respectively). These distinct trends highlight the variations in GMI kinetics with the use of different anti-fungal drugs and their implications in relation to IA treatment response. [ABSTRACT FROM AUTHOR]
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- 2014
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22. Double-Stranded RNA Mycovirus Infection of Aspergillus fumigatus Is Not Dependent on the Genetic Make-Up of the Host.
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Refos, Jeannine M., Vonk, Alieke G., Eadie, Kimberly, Lo-Ten-Foe, Jerome R., Verbrugh, Henri A., van Diepeningen, Anne D., and van de Sande, Wendy W. J.
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DOUBLE-stranded RNA , *FUNGAL viruses , *VIRUS diseases , *ASPERGILLUS fumigatus , *FUNGAL genetics , *MICROBIAL virulence - Abstract
Aspergillus fumigatus is a fungus that causes opportunistic infections in immunocompromised patients, with high morbidity and mortality. In its turn, A. fumigatus can become infected with mycoviruses. Most mycoviruses have a dsRNA genome and can cause fungal hypovirulence. For that reason, mycoviruses could theoretically be used as therapeutic tools to combat fungal infections. We determined if a certain genetic make-up of A. fumigatus was associated with the presence of mycoviruses in 86 clinical A. fumigatus isolates. Mycovirus screening was performed by isolating dsRNA from mycelial cultures using a Trizol/Chloroform method. The genetic relatedness of dsRNA infected A. fumigatus was determined by cell surface protein (CSP) typing and determination of the mating type. Sixteen (18.6%) of the 86 clinical A. fumigatus isolates contained dsRNA. The A. fumigatus collection could be divided into 11 different CSP types. DsRNA infected A. fumigatus isolates had similar CSP types as non-infected isolates. In both cases, the CSP types t01, t02, t03 and t04 were the most prevalent and the distribution comparable to the CSP types observed in other Dutch collections. Mating types MAT1-1 and MAT1-2 were evenly distributed among all A. fumigatus strains, regardless of CSP type. No difference was observed in mycovirus infections between MAT1-1 and MAT1-2 isolates. DsRNA mycovirus infections in A. fumigatus are not related to either CSP or mating type and therefore represent an interesting future therapeutic tool to combat fungal infections. [ABSTRACT FROM AUTHOR]
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- 2013
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23. Association of Eumycetoma and Schistosomiasis.
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van Hellemond, Jaap J., Vonk, Alieke G., de Vogel, Corné, Koelewijn, Rob, Vaessen, Norbert, Fahal, Ahmed H., van Belkum, Alex, and van de Sande, Wendy W. J.
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SCHISTOSOMIASIS , *MYCOSES , *DISEASE susceptibility , *ODDS ratio , *ENVIRONMENTAL exposure - Abstract
Eumycetoma is a morbid chronic granulomatous subcutaneous fungal disease. Despite high environmental exposure to this fungus in certain regions of the world, only few develop eumycetoma for yet unknown reasons. Animal studies suggest that co-infections skewing the immune system to a Th2-type response enhance eumycetoma susceptibility. Since chronic schistosomiasis results in a strong Th2-type response and since endemic areas for eumycetoma and schistosomiasis do regionally overlap, we performed a serological case-control study to identify an association between eumycetoma and schistosomiasis. Compared to endemic controls, eumycetoma patients were significantly more often sero-positive for schistosomiasis (p = 0.03; odds ratio 3.2, 95% CI 1.18–8.46), but not for toxoplasmosis, an infection inducing a Th1-type response (p = 0.6; odds ratio 1.5, 95% CI 0.58–3.83). Here, we show that schistosomiasis is correlated to susceptibility for a fungal disease for the first time. Author Summary: Eumycetoma is a mutilating fungal disease of mainly the foot and is found in (sub)tropical regions such as Sudan. At the moment it is not understood why some people develop eumycetoma and others not. In the regions were eumycetoma is prevalent many other infections are also found. These infections could alter the immune system which makes people more or less susceptible in obtaining another infection. One of the infections with such an effect is Schistosomiasis. In Africa, eumycetoma is found in regions were schistosomiasis is prevalent. In this study we show that eumycetoma patients more often have antibodies against Schistosoma species, than healthy controls from the same region. In contrast, eumycetoma patients did not have more often antibodies against Toxoplasma species. This might implicate that schistosomiasis predisposes eumycetoma development. If schistosomiasis indeed predisposes eumycetoma development, eradicating Schistosoma in a population could also lower the number of eumycetoma cases in that area, which in the end could lead to intervention strategies not only for schistosomiasis but also for eumycetoma. [ABSTRACT FROM AUTHOR]
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- 2013
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24. Aspergillus fumigatus cell wall components differentially modulate host TLR2 and TLR4 responses
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Chai, Louis Y.A., Vonk, Alieke G., Kullberg, Bart Jan, Verweij, Paul E., Verschueren, Ineke, van der Meer, Jos W.M., Joosten, Leo A.B., Latgé, Jean-Paul, and Netea, Mihai G.
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ASPERGILLUS fumigatus , *FUNGAL cell walls , *NATURAL immunity , *CHITIN , *GLUCANS , *POLYSACCHARIDES , *INTERLEUKIN-6 , *IMMUNOREGULATION , *PATHOGENIC microorganisms - Abstract
Abstract: Aspergillus fumigatus conidia attenuates host proinflammatory responses through modulation of Toll-like receptor (TLR)2 and TLR4 signaling, but the precise mechanisms that mediate this effect are not known. In the present study, the role of the Aspergillus cell wall polysaccharide constituents responsible for the modulation of host capability to mount a proinflammatory response was studied. Aspergillus cell wall fractions and its major components showed differential capabilities in modulating host TLR-mediated interleukin (IL)-6 production. Beta-glucan specifically suppressed TLR4-induced response, while alpha-glucan inhibited IL-6 induced through TLR2- and TLR4-stimulation. Galactomannan diminished TLR4-mediated response, while its inhibitory effects on TLR2-signaling were limited. Chitin, on the other hand, did not have significant immunomodulatory capability. The ability of the fungal cell wall to alter the immune signature of the pathogen may contribute to its virulence and the pathogenesis of co-infection. [ABSTRACT FROM AUTHOR]
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- 2011
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25. Fungal strategies for overcoming host innate immune response.
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Chai, Louis Y. A., Netea, Mihai G., Vonk, Alieke G., and Kullberg, Bart-Jan
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A successful pathogen is one that is able to effectively survive and evade detection by the host innate immune defense. Fungal pathogens have adopted strategies which evade host defense and eventually cause disease in at-risk patients. Shielding of stimulatory surface recognition molecules, shedding of decoy components, induction of anti-inflammatory signals, complement evasion and resilient survival capacity are successful evasion mechanisms employed by fungal pathogens. Understanding these complex pathways of immune evasion can potentially contribute to development of novel therapeutic strategies against fungal infections. [ABSTRACT FROM AUTHOR]
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- 2009
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26. Influence of endogenous pro-inflammatory cytokines on neutrophil-mediated damage of Candida albicans pseudohyphae, quantified in a modified tetrazolium dye assay.
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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
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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]
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- 2005
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27. Apolipoprotein-E-deficient mice exhibit an increased susceptibility to disseminated candidiasis.
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Vonk, Alieke G., De Bont, Natasja, Netea, Mihai G., Demacker, Pierre N. M., Van Der Meer, Jos W. M., Stalenhoef, Anton F. H., and Kullberg, Bart Jan
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CANDIDA albicans , *CANDIDIASIS , *MYCOSES , *APOLIPOPROTEIN E , *APOLIPOPROTEINS , *MICE - Abstract
The effect of hyperlipoproteinemia on systemic candidiasis was investigated by assessing the susceptibility of hyperlipoproteinemic, apolipoprotein E (ApoE)-deficient (ApoE-/-) mice to a systemic Candida albicans infection. The absence of ApoE in these mice resulted in an eightfold increase in plasma lipoprotein concentrations in the very low-density lipoprotein (VLDL) fraction, as compared with levels seen in ApoE+/+ mice. Mortality due to candidemia was significantly higher (86%) in ApoE-/- mice than in ApoE+/+ mice (52%), and in platings of homogenized kidney material on fungal culture medium, ApoE-/- mice yielded significantly higher levels of C. albicans outgrowth than did ApoE+/+ mice. C. albicans grew twofold better in ApoE-/- plasma in 4 h than in ApoE+/+ plasma, and depletion of lipoproteins from plasma resulted in a significant seven- to tenfold increase in C. albicans growth. Recombinant ApoE did not directly inhibit C. albicans growth. Our data indicate that the increased susceptibility of ApoE-/- mice to C. albicans is due both to increased growth of blastoconidia in ApoE-/- mice in response to the availability of lipids as nutrients, and to the neutralization of candidacidal factors by lipoproteins. This study suggests that lipoproteins play a significant role in host defense against candidiasis. [ABSTRACT FROM AUTHOR]
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- 2004
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28. Differential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infection.
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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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29. Delayed Clearance of Intraabdominal Abscesses Caused by Candida albicans in Tumor Necrosis Factor-α-and Lymphotoxin-α-Deficient Mice.
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Vonk, Alieke G., Netea, Mihai G., van Krieken, Johan H., van der Meer, Jos W.M., and Kullberg, Bart Jan
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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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30. 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
- Published
- 1999
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31. Mycovirus therapy for invasive pulmonary aspergillosis?
- Author
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van de Sande WWJ and Vonk AG
- Subjects
- Animals, Humans, Aspergillus growth & development, Aspergillus virology, Biological Therapy methods, Fungal Viruses growth & development, Invasive Pulmonary Aspergillosis therapy
- Abstract
With the current revived interest in the use of bacteriophages for the treatment of bacterial infections, the study of mycoviruses as novel therapeutic solutions for invasive aspergillosis is the logical next step. Although ssRNA, dsRNA, and ssDNA mycoviruses have been identified, the majority of characterised mycoviruses have dsRNA genomes. Prevalence of dsRNA mycoviruses in Aspergillus spp. varies, and mycoviruses can have different effects on their fungal hosts: hypovirulence, hypervirulence, or a killer phenotype. Therapeutically, extracellular transmission of the mycovirus is essential. DsRNA mycoviruses lack an extracellular phase; however, a single ssDNA mycovirus with homologues in Aspergillus genomes has been described with an extracellular mode of transmission. Mycoviruses can induce hypovirulence or a killer phenotype, and both can be exploited therapeutically. Mycoviruses inducing hypovirulence have been used to control chestnut blight, however for aspergillosis no such mycovirus has been identified yet. Mycovirus encoded killer toxins or anti-idiotypic antibodies and killer peptides derived from these have been demonstrated to control fungal infections including aspergillosis in animals. This indicates that mycoviruses inducing both phenotypes could be exploited therapeutically as long as the right mycovirus has been identified., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)
- Published
- 2019
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32. Chitinase Induction Prior to Caspofungin Treatment of Experimental Invasive Aspergillosis in Neutropenic Rats Does Not Enhance Survival.
- Author
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Refos JM, Vonk AG, Ten Kate MT, Verbrugh HA, Bakker-Woudenberg IAJM, and van de Sande WWJ
- Subjects
- Animals, Antifungal Agents pharmacology, Aspergillus fumigatus drug effects, Aspergillus fumigatus pathogenicity, Chitosan chemistry, Chitosan pharmacology, Disease Models, Animal, Female, Invasive Pulmonary Aspergillosis metabolism, Invasive Pulmonary Aspergillosis prevention & control, Lung drug effects, Lung enzymology, Microbial Sensitivity Tests, Molecular Weight, Neutropenia microbiology, Rats, Aspergillus fumigatus metabolism, Caspofungin pharmacology, Chitinases metabolism, Invasive Pulmonary Aspergillosis drug therapy, Neutropenia complications
- Abstract
Host 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. fumigatus and 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. fumigatus and 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., (Copyright © 2017 American Society for Microbiology.)
- Published
- 2017
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33. Validation of a new Aspergillus real-time PCR assay for direct detection of Aspergillus and azole resistance of Aspergillus fumigatus on bronchoalveolar lavage fluid.
- Author
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Chong GL, van de Sande WW, Dingemans GJ, Gaajetaan GR, Vonk AG, Hayette MP, van Tegelen DW, Simons GF, and Rijnders BJ
- Subjects
- Aspergillus drug effects, Cytochrome P-450 Enzyme System genetics, Female, Fungal Proteins genetics, Humans, Invasive Pulmonary Aspergillosis diagnosis, Invasive Pulmonary Aspergillosis microbiology, Male, Molecular Diagnostic Techniques methods, Mutant Proteins genetics, Mutation, Missense, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Antifungal Agents pharmacology, Aspergillus isolation & purification, Azoles pharmacology, Bronchoalveolar Lavage Fluid microbiology, Microbiological Techniques methods, Multiplex Polymerase Chain Reaction methods, Real-Time Polymerase Chain Reaction methods
- Abstract
Azole resistance in Aspergillus fumigatus is 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 Aspergillus species, and one that detects the TR34, L98H, T289A, and Y121F mutations in CYP51A and differentiates susceptible from resistant A. fumigatus strains. 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 Aspergillus was <36. Sixteen of the 19 BAL fluid samples had a positive PCR (2 Aspergillus species and 14 A. fumigatus samples). 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 Aspergillus species directly from BAL fluid samples. More importantly, this assay detects and differentiates wild-type from resistant strains, even if BAL fluid cultures remain negative., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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34. Double-stranded RNA mycovirus infection of Aspergillus fumigatus is not dependent on the genetic make-up of the host.
- Author
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Refos JM, Vonk AG, Eadie K, Lo-Ten-Foe JR, Verbrugh HA, van Diepeningen AD, and van de Sande WW
- Subjects
- Aspergillus fumigatus genetics, Aspergillus fumigatus metabolism, Mycelium genetics, Mycelium metabolism, RNA Viruses genetics, RNA, Double-Stranded genetics, RNA, Viral genetics, Aspergillus fumigatus virology, Mycelium virology, RNA Viruses metabolism, RNA, Double-Stranded metabolism, RNA, Viral metabolism
- Abstract
Aspergillus fumigatus is a fungus that causes opportunistic infections in immunocompromised patients, with high morbidity and mortality. In its turn, A. fumigatus can become infected with mycoviruses. Most mycoviruses have a dsRNA genome and can cause fungal hypovirulence. For that reason, mycoviruses could theoretically be used as therapeutic tools to combat fungal infections. We determined if a certain genetic make-up of A. fumigatus was associated with the presence of mycoviruses in 86 clinical A. fumigatus isolates. Mycovirus screening was performed by isolating dsRNA from mycelial cultures using a Trizol/Chloroform method. The genetic relatedness of dsRNA infected A. fumigatus was determined by cell surface protein (CSP) typing and determination of the mating type. Sixteen (18.6%) of the 86 clinical A. fumigatus isolates contained dsRNA. The A. fumigatus collection could be divided into 11 different CSP types. DsRNA infected A. fumigatus isolates had similar CSP types as non-infected isolates. In both cases, the CSP types t01, t02, t03 and t04 were the most prevalent and the distribution comparable to the CSP types observed in other Dutch collections. Mating types MAT1-1 and MAT1-2 were evenly distributed among all A. fumigatus strains, regardless of CSP type. No difference was observed in mycovirus infections between MAT1-1 and MAT1-2 isolates. DsRNA mycovirus infections in A. fumigatus are not related to either CSP or mating type and therefore represent an interesting future therapeutic tool to combat fungal infections.
- Published
- 2013
- Full Text
- View/download PDF
35. Unrecognized norovirus infections in health care institutions and their clinical impact.
- Author
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Beersma MF, Sukhrie FH, Bogerman J, Verhoef L, Mde Melo M, Vonk AG, and Koopmans M
- Subjects
- Adult, Child, Child, Preschool, Feces virology, Female, Humans, Incidence, Male, RNA, Viral genetics, RNA, Viral isolation & purification, Real-Time Polymerase Chain Reaction, Tertiary Care Centers, Caliciviridae Infections epidemiology, Caliciviridae Infections virology, Cross Infection epidemiology, Cross Infection virology, Gastroenteritis epidemiology, Gastroenteritis virology, Norovirus isolation & purification
- Abstract
Noroviruses (NoVs) have emerged as the leading cause of acute viral gastroenteritis (GE) in humans. Although diagnostic facilities have greatly improved, significant underdiagnosis of NoV in hospitals may still occur, thereby increasing clinical burden and nosocomial spread. We evaluated the underdiagnosis of sporadic NoV infections in a tertiary care hospital and estimated its clinical impact. From December 2008 until July 2009, fecal samples specifically referred for bacterial but not viral examination were retrospectively tested for NoV by real-time PCR. The clinical and virological data from patients with undiagnosed NoV infection (missed patients) were evaluated and compared with those from patients with recognized NoV. During the study period, 45 patients with undiagnosed NoV were detected, whereas 50 patients were regularly diagnosed. The missed NoV cases were more frequently adults than children (80% versus 46%; P < 0.001). The viral load levels did not differ between the diagnosed and missed patients, but missed patients more frequently presented without diarrhea (20% versus 4%; P < 0.07). The newly admitted missed NoV cases with GE underwent more diagnostic imaging (24% versus 4%; P < 0.01) and tended to be hospitalized longer. When missed-NoV patients were included, the number of nosocomial clusters doubled and missed patients were index cases in 5 of the 6 clusters. These data indicate that NoV infections are frequently missed despite routine laboratory testing and demonstrate that underdiagnosis of NoV patients is associated with costly abdominal imaging and nosocomial clustering. Awareness of NoV infection in adult patients and education about the importance of viral GE should be increased.
- Published
- 2012
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36. Early serum galactomannan trend as a predictor of outcome of invasive aspergillosis.
- Author
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Chai LY, Kullberg BJ, Johnson EM, Teerenstra S, Khin LW, Vonk AG, Maertens J, Lortholary O, Donnelly PJ, Schlamm HT, Troke PF, Netea MG, and Herbrecht R
- Subjects
- Female, Galactose analogs & derivatives, Humans, Invasive Pulmonary Aspergillosis drug therapy, Invasive Pulmonary Aspergillosis mortality, Male, Prognosis, ROC Curve, Survival Analysis, Time Factors, Treatment Outcome, Biomarkers blood, Drug Monitoring methods, Invasive Pulmonary Aspergillosis diagnosis, Mannans blood, Serum chemistry
- Abstract
The monitoring and prediction of treatment responses to invasive aspergillosis (IA) are difficult. We determined whether serum galactomannan index (GMI) trends early in the course of disease may be useful in predicting eventual clinical outcomes. For the subjects recruited into the multicenter Global Aspergillosis Study, serial GMIs were measured at baseline and at weeks 1, 2, and 4 following antifungal treatment. Clinical response and survival at 12 weeks were the outcome measures. GMI trends were analyzed by using the generalized estimation equation approach. GMI cutoffs were evaluated by using receiver-operating curve analyses incorporating pre- and posttest probabilities. Of the 202 study patients diagnosed with IA, 71 (35.1%) had a baseline GMI of ≥ 0.5. Week 1 GMI was significantly lower for the eventual responders to treatment at week 12 than for the nonresponders (GMIs of 0.62 ± 0.12 and 1.15 ± 0.22, respectively; P = 0.035). A GMI reduction of >35% between baseline and week 1 predicted a probability of a satisfactory clinical response. For IA patients with pretreatment GMIs of <0.5 (n = 131; 64.9%), GMI ought to remain low during treatment, and a rising absolute GMI to >0.5 at week 2 despite antifungal treatment heralded a poor clinical outcome. Here, every 0.1-unit increase in the GMI between baseline and week 2 increased the likelihood of an unsatisfactory clinical response by 21.6% (P = 0.018). In summary, clinical outcomes may be anticipated by charting early GMI trends during the first 2 weeks of antifungal therapy. These findings have significant implications for the management of IA.
- Published
- 2012
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- View/download PDF
37. Phagocytosis and intracellular killing of Candida albicans by murine polymorphonuclear neutrophils.
- Author
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Vonk AG, Netea MG, and Kullberg BJ
- Subjects
- Animals, Mice, Neutrophils cytology, Candida albicans cytology, Candida albicans immunology, Microbial Viability, Neutrophils immunology, Phagocytosis
- Abstract
Polymorphonuclear neutrophils (PMNs) are important phagocytes in the control of Candida infections. The phagocytic contribution of PMNs to host defence can by assessed by various methods, such as microbiological assays. However, assessment and definition of intracellular killing capacity can be a source of considerable confusion. A comparison of the growth of Candida in the presence of PMN with the growth of Candida in phagocyte-free suspensions may lead to an overestimation of killing capacity because PMNs can use both intracellular and extracellular killing mechanisms. Here, we describe the use of an adherent monolayer of exudate peritoneal PMNs that is used to differentiate between the process of phagocytosis and intracellular killing.
- Published
- 2012
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- View/download PDF
38. Modulation of Toll-like receptor 2 (TLR2) and TLR4 responses by Aspergillus fumigatus.
- Author
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Chai LY, Kullberg BJ, Vonk AG, Warris A, Cambi A, Latgé JP, Joosten LA, van der Meer JW, and Netea MG
- Subjects
- Humans, Hyphae immunology, Immune Tolerance, Interleukin-1beta biosynthesis, Interleukin-6 biosynthesis, Spores, Fungal immunology, Aspergillus fumigatus immunology, Interleukin-1beta antagonists & inhibitors, Interleukin-6 antagonists & inhibitors, Toll-Like Receptor 2 immunology, Toll-Like Receptor 4 immunology
- 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-1beta proinflammatory responses in human mononuclear cells with suppression of IL-1beta 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
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- View/download PDF
39. 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
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40. Endogenous interleukin (IL)-1 alpha and IL-1 beta are crucial for host defense against disseminated candidiasis.
- Author
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Vonk AG, Netea MG, van Krieken JH, Iwakura Y, van der Meer JW, and Kullberg BJ
- Subjects
- Animals, Candida albicans immunology, Candidiasis microbiology, Candidiasis mortality, Candidiasis pathology, Disease-Free Survival, Immunocompetence immunology, Interferon-gamma metabolism, Kidney microbiology, Kidney pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Spleen cytology, Candida albicans pathogenicity, Candidiasis immunology, Interleukin-1 immunology
- Abstract
Background: Interleukin (IL)-1 alpha and IL-1 beta are protective proinflammatory cytokines involved in host defense against Candida albicans. 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., Methods: Mice deficient in the genes encoding IL-1 alpha (IL-1 alpha-/-), IL-1 beta (IL-1 beta-/-), or both molecules (IL-1 alpha-/- beta-/-) were used. Survival and C. albicans outgrowth in the kidneys was assessed after intravenous injection of C. albicans., Results: Both mortality and C. albicans outgrowth in the kidneys were significantly increased in IL-1 alpha-/- and IL-1 beta-/- mice, compared with those in control mice, with the IL-1 alpha-/- beta-/- mice being most susceptible to disseminated candidiasis. The host defense mechanisms triggered by IL-1 alpha and IL-1 beta differed from one another. IL-1 beta-/- mice showed decreased recruitment of granulocytes in response to an intraperitoneal C. albicans challenge, and generation of superoxide production was diminished in IL-1 beta-/- granulocytes. IL-1 alpha-/- mice had a reduced capacity to damage C. albicans pseudohyphae. Protective type 1 responses were deficient in both IL-1 alpha-/- and IL-1 beta-/- mice, as assessed by production of interferon-gamma by splenocytes in response to heat-killed C. albicans., Conclusion: Although IL-1 alpha and IL-1 beta have differential effects on the various arms of host defense, both cytokines are essential for mounting a protective host response against invasive C. albicans infection.
- Published
- 2006
- Full Text
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41. Effect of recombinant murine granulocyte colony-stimulating factor with or without fluoroquinolone therapy on mixed-infection abscesses in mice.
- Author
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Stearne LE, Vonk AG, Kullberg BJ, and Gyssens IC
- Subjects
- Abscess microbiology, Animals, Anti-Infective Agents pharmacology, Aza Compounds pharmacology, Aza Compounds therapeutic use, Bacillus pathogenicity, Colony Count, Microbial, Cytokines metabolism, Escherichia coli pathogenicity, Female, Fluoroquinolones pharmacology, Granulocyte Colony-Stimulating Factor pharmacology, Mice, Mice, Inbred BALB C, Microbial Sensitivity Tests, Moxifloxacin, Quinolines pharmacology, Quinolines therapeutic use, Recombinant Proteins, Spleen microbiology, Survival Analysis, Treatment Outcome, Abscess drug therapy, Anti-Infective Agents therapeutic use, Fluoroquinolones therapeutic use, Granulocyte Colony-Stimulating Factor therapeutic use
- Abstract
The aim of the study was to determine if immunomodulation of host defense with recombinant murine granulocyte colony-stimulating factor (G-CSF) improves the efficacy of trovafloxacin or moxifloxacin in abscesses containing Bacillus fragilis ATCC 23745 and different Escherichia coli strains varying in virulence. Treatment of mice inoculated with 10(7) CFU B. fragilis and 10(5) CFU low-virulence E. coli with either trovafloxacin (150 mg/kg/day every 24 hours, days 3 to 7) or moxifloxacin (96 mg/kg/day every 12 hours, days 3 to 7), significantly reduced the number of B. fragilis to 6.9 +/- 0.35 and 5.8 +/- 0.10 and that of E. coli to 4.9 +/- 0.09 and 4.2 +/- 0.07 log CFU/abscess for trovafloxacin and moxifloxacin, respectively, compared to controls (B. fragilis 8.7 and E. coli 7.4 log CFU/abscess) on day 8. Also, moxifloxacin was more potent than trovafloxacin. Addition of G-CSF prophylaxis (1 mug once on day -1) or therapy (1 mug/day on days 3 to 7) to fluoroquinolone treatment did not improve the efficacy of fluoroquinolone therapy alone. The effect of moxifloxacin with or without G-CSF prophylaxis on abscesses with a virulent hemolytic E. coli strain was also studied. In moxifloxacin-treated mice, 75% survived infection compared to 10% of controls. Combining moxifloxacin with G-CSF prophylaxis significantly decreased survival (30%) compared to moxifloxacin alone. In addition, G-CSF prophylaxis resulted in a threefold (E. coli) to 100-fold (B. fragilis) increased outgrowth in the abscesses of surviving mice. 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.
- Published
- 2005
- Full Text
- View/download PDF
42. 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
43. Phagocytosis and intracellular killing of Candida albicans blastoconidia by neutrophils and macrophages: a comparison of different microbiological test systems.
- Author
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Vonk AG, Wieland CW, Netea MG, and Kullberg BJ
- Subjects
- Animals, Female, Humans, Macrophages, Peritoneal immunology, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mycology methods, Neutrophils immunology, Candida albicans physiology, Macrophages, Peritoneal microbiology, Neutrophils microbiology, Phagocytosis immunology
- Abstract
Polymorphonuclear neutrophils (PMN) and mononuclear phagocytes represent an important first line and effector function in the control of Candida infections. Their relative contribution to host defence is frequently assessed by means of microbiological assays. However, reported results are divergent and might well be associated with study design-related issues. In the present study, we compared frequently used microbiological candidacidal assays, with the purpose of determining the most adequate method for assessment of phagocytosis and intracellular killing. We concluded that microbiological assays using yeast-phagocyte suspensions are inappropriate for the assessment of intracellular killing of Candida blastoconidia by murine macrophages, due to adherence or clumping of cells. In contrast, an adherent monolayer of phagocytes can be applied as a single microbiological assay to independently study the process of phagocytosis and intracellular killing, by exudate peritoneal macrophages as well as exudate peritoneal PMN.
- Published
- 2002
- Full Text
- View/download PDF
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