A dissertation in partial compliance with the Master's Diploma in Technology: Homoeopathy, Technikon Natal, 1996. / The aim of the study was to establish the effect of a Helonias complex on the growth of Candida albicans in vitro in terms of growth rate, maximum specific growth rate, latent period before maximum specific growth rate and percentage germ tube production so as to establish the area of action of homoeopathic remedies / M

Candida albicans is a polymorphic yeast that can cause life threatening systemic infections in immuno-compromised individuals. One key attribute of C. albicans that enhances its pathogenicity is the ability to switch morphologies between filamentous and vegetative modes in response to specific environmental conditions. Stressful changes in such cellular conditions commonly cause a rapid inhibition of global protein synthesis leading to altered programmes of gene expression. In Saccharomyces cerevisiae, fusel alcohols signal nitrogen scarcity and induce pseudohyphal growth enabling yeast colonies to spread towards nutrient replete areas. These alcohols also inhibit protein synthesis by targeting the translation initiation factor, eIF2B. eIF2B is the guanine nucleotide exchange factor for eIF2, which supports eIF2-GTP production and represents a key regulated step in translation initiation. eIF2-GTP interacts with Met-tRNAiMet to form the ternary complex which is essential for translation initiation. Fusel alcohols target eIF2B leading to reduced levels of ternary complex and reduced protein synthesis. In Candida albicans, a variety of cell biological and genetic assays suggest that fusel alcohols and ethanol inhibit protein synthesis by targeting the translation initiation factor, eIF2B, and they also induce hyphal/pseudohyphal growth, a process that is associated with pathogenesis in C. albicans. In contrast to fusel alcohols, farnesol, aquorum sensing alcohol, does not appear to impact upon eIF2B activity. Rather, biochemical and mass spectrometric analysis suggest farnesol affects the interaction of the mRNA with the small ribosomal subunit during translation initiation. Further elucidation of the effect of farnesol on C. albicans transcript levels and ribosome association by next generation sequencing gave insight into the genes that are differentially expressed following farnesol treatment. While genes involved inmorphological differentiation were generally repressed, those involved in protein synthesis were upregulated, possibly as an adaptive response to inhibition of protein synthesis by farnesol. Intriguingly, the regulation of these functional categories of genes occurred in a co-ordinated manner at either the transcript level or at the level of ribosome association, but rarely was gene expression regulated at both transcriptional and post-transcriptional levels for the same gene.

Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista / Introducción: La Diabetes mellitus tipo 2 (DM2) es una enfermedad crónica altamente prevalente que debe ser rigurosamente monitoreada para evitar complicaciones asociadas a su descompensación, la cual es establecida cuando los sujetos presentan valores de Hemoglobina glicosilada (HbA1c) mayores a 7%. Esto puede asociarse a una acidificación del pH salival, lo que afectaría el crecimiento y diferenciación de levaduras del género Candida provocando aparición de Candidiasis. Es relevante determinar número y especies de levaduras presentes en saliva de pacientes diabéticos y la susceptibilidad de éstas a los distintos antifúngicos para mejorar el enfoque terapéutico. Materiales y Métodos: Se recogieron muestras de saliva no estimulada de 52 pacientes con DM2 de la Asociación de diabéticos de Chile (ADICH). Se les midió pH salival y se cultivaron en placas de Agar Sabouraud, realizando el recuento de colonias en UFC/ml. Se identificaron las especies en forma presuntiva en CHROMAgar Candida® confirmándose luego mediante PCR con partidores específicos. Se cultivaron los aislados de C.Albicans en Agar Sabouraud Tetraciclina con discos de difusión de Nistatina y Fluconazol para medir la susceptibilidad en milímetros. Se utilizó el test de Spearman para correlacionar las variables HbA1c, pH salival y cantidad de UFC/ml; también para HbA1c y susceptibilidad en mm. a los distintos antifúngicos, t-test para comparar ambos grupos y la prueba de Chi cuadrado para comparar valores entre pacientes compensados y no compensados. Se consideraron estadísticamente significativos valores de p < 0,05. Resultados: El 50% de los pacientes estaban descompensados. El 66% del total de levaduras aisladas fue Candida albicans, 43,6% Candida no albicans, destacando C. Glabrata. En pacientes con DM2 descompensada, se observó asociación inversa entre valores de HbA1c y pH salival. A mayor acidificación salival se observó mayor diversidad y cantidad de levaduras del género Candida. No se observó relación entre valores de HbA1c y susceptibilidad a nistatina o fluconazol. Se observó una leve correlación inversa entre pH salival y susceptibilidad a nistatina. Conclusión: La descompensación metabólica en pacientes con DM2 puede resultar en acidificación del pH salival afectando la cuantificación, diversidad de levaduras y la susceptibilidad de éstas a la terapia antifúngica. / Adscrito a Proyecto FIOUCH 13-002

Orientador: Ramon Kaneno / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-04T01:09:50Z (GMT). No. of bitstreams: 1 Martins_PriscilaRaquel_M.pdf: 3935077 bytes, checksum: a342a73cd22f638b9ca5c0901503c580 (MD5) Previous issue date: 2004 / Resumo: A atividade imunomoduladora de cogumelos medicinais é atribuída principalmente às J}-glucanas. Neste estudo, avaliamos o efeito de peptidoglucanas extraídas do cogumelo Agaricus blazei (ATF) quanto à atividade candidacida, expressão de receptores de manose e produção de H2O2 e NO por macrófagos peritoneais murinos. Camundongos normais BALB/c receberam três inoculações intraperitoneais de solução salina (grupo controle) ou fração ATF (grupo ATF) e após 48 horas os macrófagos peritoneais foram coletados e ensaiados contra leveduras de Candida albicans. Nossos resultados indicam que o tratamento aumentou a atividade candidacida de macrófagos, produção de H2O2e expressão de receptores de manose, contudo, o tratamento não alterou a produção de NO. Nossos resultados sugerem que a fração ATF pode aumentar a resistência contra agentes infecciosos devido à estimulação da atividade microbicida de macrófagos / Abstract: Immunomodulatory activity of medicinal mushrooms is attributed to glucans. In the present study we avaluated the eifect of peptidoglycans of Agaricus blazei (ATF) on the candidacidal activity, the expression of mannose receptors (MR), production of H2O2 and NO by murine peritoneal macrophages. Normal BALB/c mice were i.p. treated with 3 inoculations of ATF (ATF group) or salt solution (control group) and after 48hr peritoneal macrophages were assayed against Candida albicans yest forms. Our results indicated that the treatment enhanced the candidacidal activity of peritoneal macrophages and increased the H2O2 production and MR expression. However ATF was not able to increase the spontaneous production of NO. The results suggest that ATF can enhance the host resistence against infectious agents due to the stimulation of the microbicidal activity of macrophages / Mestrado / Mestre em Farmacologia

Orientador: Antonio Olavo Cardoso Jorge / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-24T02:33:03Z (GMT). No. of bitstreams: 1 Totti_MarildaAparecidaGoncalves_D.pdf: 5573911 bytes, checksum: db09b48095e15ef68b81ad95bb3c3fac (MD5) Previous issue date: 1998 / Resumo: A presença de Candida albicans e o desenvolvimento de candidose na cavidade bucal de camundongos normais e xerostômicos foram avaliados após uma e quatro inoculações com 108 células viáveis de C. albicam; na boca dos animais. A xerostomia foi obtida pela retirada das glândulas salivares maiores dos camundongos (sialoadenectomia) e a recuperação da levedura foi realizada após 1, 2, 3,5, 8, 15 dias e a seguir intervalos regulares de 15 dias. A comprovação da levedura recuperada foi feita através de identificação da espécie e da verificação do fator killer. Candidose foi verificada no epitélio de 6 regiões do dorso da língua dos camundongos em cortes histológicos sagitais corados por H.E e P.A.S. Os resultados obtidos demonstraram: a) que a xerostomia produzida pela sialoadenectomia em camundongos, propiciou recuperação de C. albicans na cavidade bucal dos animais, em maior número e por períodos mais prolongados; b) as quantidades de C. albicans na cavidade bucal de camundongos sialoadenectomizados foram maiores estatisticamente significativas nas recuperações de 30 até 195 dias após 4 inoculações da levedura; c) candidose ocorreu em maior número de animais e as lesões foram mais extensas nos camundongos sialoadenectomizados, em relação aos normais / Abstract: The presence of Candida albicans and candidosis development in the oral cavity of normal and sialoadenectomized mice were evaluated after one and four inoculations, with 108 viable cells of C. albicans in the mouth of the animals. The xerostomia was obtained by surgical removal of the major salivary glands from mice (sialoadenectomy) and the recovery of the yeast was accomplished after 1, 2, 3, 5, 8, 15 days and then in intervals of 15 days. The confirmation of the yeast recovered was established through identification of the species and the verification of the killer factor. Candidosis was verified in the epithelium of six are as of the dorsal mice tongue in sagital histological sections stained with hematoxylin & eosin and periodic acid-Schifr. The results obtained showed: a) that xerostomia produced by the sialoadenectomy in the mice propitiated recovery of C. albicans in the oral cavity of the animals in higher number and for more wide periods; b) The quantity of C. Albicans in the oral cavity of sialoadenectomized mice were larger and statistically significant in the recoveries of 30 to 195 days after four inoculations of the yeast; c) candidosis occured in higher number of animals and the lesions were more extensive in the sialoadenectomized mice in relation to the normal / Doutorado / Biologia e Patologia Buco-Dental / Doutor em Odontologia

Orientador: Antonio Olavo Cardoso Jorge / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-19T08:44:03Z (GMT). No. of bitstreams: 1 Totti_MarildaAparecidaGoncalves_M.pdf: 2950217 bytes, checksum: 8656561b666ad4485dcb6dafe09fdf85 (MD5) Previous issue date: 1994 / Resumo: A presença de cinco espécies de Candida foi estudada em ratos normais e xerostômicos. Os animais foram inoculados na cavidade bucal durante 4 dias consecutivos com '10 POT.8' células de C. albicans, C. parapsilosis, C. Tropicalis, C. Guilliermondii e C. Krusei. Após 1. 2. 3. 5. 8. 15 e 30 dias da última inoculação, as leveduras foram recuperadas da saliva e quantificadas. C. albicans foi a única espécie recuperada em maior quantidade da boca dos ratos sialoadenectomizados em relação aos normais. C. Tropicalis, C. guilliermondii e C. krusei permaneceram na boca de ratos normais e sialoadenectomizados pelo período de até 5 dias, enquanto a C albicans e C. parapsilosis foram recuperadas em todos os períodos experimentais. Estes resultados confirmam que a xerostomia facilita a instalação, proliferação e persistência de C. albicans na cavidade bucal de ratos, não interferindo, porém, nas outras espécies. Os dados deste estudo sugerem que fatores inerentes às espécies atuam no processo de colonização do fungo na boca de ratos, resultando em diferentes graus de patogenicidade / Abstract: The presence of five Candida species was studied in the mouth of normal and xerostomic rats. The animals were innoculated into the oral cavity with '10 POT.8' cells of Candida albicans, C. Parapsitosis, C. Tropicalis, C. Guilliermondii and C. krusei during 4 consecutive days. The yeasts were recovered from saliva 1. 2. 3. 5. 8. 15 and 30 days after the last innoculation and quantified. C. albicans was the only specie recovered in higher quantity from sialoadenectomized rats, C. Tropicalis, C. Guilliermondii and C. krusei were recovered from the mouth of normal and sialoadenectomized rats up to 5 days after innoculation and C. albicans and C. parapsilosis in all periods. These results confirm that xerostomia facilitate the instalation, proliferation and persistence of C. albicans in the rat's oral cavity, but doesn't interfere with the other species. These differences suggest that factors inherent to the Candida species are relevant for colonization of the mouth of rats, resulting in different degrees of patogenicity / Mestrado / Mestre em Biologia e Patologia Buco-Dental

The main aim of the study was to isolate compounds active against Candida albicans from the most active species from a pool of several trees. Seven tree species with good antifungal activity were selected from the Phytomedicine Programme database. The selected plant species investigated were screened for growth inhibitory activity against Candida albicans using bioautography and serial microplate dilution methods. These tree species were: Cussonia zuluensis, Vepris reflexa, Curtisia dentata, Trichilia emetica, Terminalia phanerophlebia, Terminalia sambesiaca and Kigelia africana. Using the serial microplate dilution method for the determination of minimal inhibitory concentrations, Terminalia phanerophlebia and <i.T. sambesiaca were active against Candida albicans with MIC values as low 0.02 mg/ml. The acetone and dichloromethane extracts of all plant leaves were active against C. albicans with MICs varying from 0.02-2.5 mg/ml. Based on bioautography, the acetone extract of the leaves of Curtisia dentate had more active (5) compounds against C. albicans than any of the tree species investigated. The dichloromethane, acetone and hexane extracts of the seven tree species were further screened for antifungal activity using other fungal test organisms. The fungal species used were Aspergillus fumigatus, Microsporum canis, Sporothrix schenckii and Cryptococcus neoformans. Extracts of Curtisia dentata, Terminalia sambesiaca and Terminalia phanerophlebia had the highest activities against these fungal test organisms with minimal inhibitory concentration (MIC) values as low as 0.02 mg/ml. Cussonia zuluensis was the least active with high MIC values (>250 µg/ml in some cases) and the lowest number (1) of active chemical components on bioautograms. The highest number of active compounds (5) against C. albicans on bioautograms was observed in the acetone extracts of C. dentate. The plant species were further investigated for presence of antibacterial compounds, using Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa as test bacterial organisms. Compounds with similar Rf values in the acetone extract of C. dentate were active against both bacterial and fungal test organisms, suggesting that the growth inhibitory activity of C. dentate extracts was non-selective. C. dentate was chosen for isolation of compounds due to 1) the highest number of active compounds on bioautogram against C. albicans, 2) the MIC values (0.12-0.6 mg/ml) against C. albicans. Acetone extracts of the leaves, stem bark and twigs of Curtisia dentate were compared for antibacterial and antifungal activity using the serial microplate dilution and bioautography methods in order to select the plant part to isolate compounds from. The TLC fingerprints of the twigs and leaves were largely similar. A non-polar compound and two medium polarity compounds, present in the leaves and twigs, were missing in the stem bark extract. Bioautography indicated that the leaves contained more antibacterial and antifungal compounds than the stem bark extracts. Extracts of the leaves were 5-fold more active than the stem bark extracts against Candida albicans, with total activities of 1072 and 190 ml/g, respectively. Against bacterial test organisms extracts of the leaves, stem bark and twigs resulted in comparable activities. These findings encourage the interchangeable usage of the stem bark, leaves and twigs of this plant, which may lead to sustainable harvesting of the species. This approach may conserve this and other threatened or endangered plant species. The leaves of Curtisia dentate (Cornaceae) were serially extracted with solvents of varying polarities, starting with hexane, then dichloromethane, followed by acetone with methanol completing the fractionation. The dichloromethane (DCM) and acetone bulk fractions of Curtisia dentate contained the highest number of active compounds and resulted in low MIC values. The hexane and the methanol bulk fractions were the least active. In the hexane bulk fraction, bioautography revealed the presence of one active compound. The DCM bulk fraction showed cytotoxicity against Vero cells similar to the positive control, berberine with an LC50 value of 10 µg/ml. The acetone and dichloromethane fractions resulted in total activity values of 3312 and 4240 ml, respectively. However, these fractions were cytotoxic to the Vero cells with LC50 values of 24.4 µg/ml for acetone fraction and 6.6 µg/ml for the dichloromethane fraction. The cytotoxicity data may serve to discourage the use of these extracts to treat candidosis. However, preparations of these fractions may be used topically on wounds to combat infections. The application of these extracts on rat wound model did not result in any observable pathologies. The DCM and acetone bulk fractions each contained 4 compounds active against Candida albicans. Only the dichloromethane extract was fractionated as these extracts contained almost similar active compounds. Column chromatography using silica as the stationary phase afforded four compounds from the DCM extract. These compounds were identified using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) as lupeol (CI), betulinic acid (CII), ursolic acid (CIII) and hydroxyl-ursolic acid (CIV). These compounds have been isolated from several plant species and have been to be found active against several pathogens including the human immunodeficiency virus (HIV). This is the first report of the isolation of these compounds from Curtisia dentate. The antibacterial activity of these compounds have been reported. The anti-Candida activity of ursolic oleanolic and ursolic acid has been reported with MIC values exceeding 128 µg/ml (Hiriuchi et al., 2007). However, the anti-Candida activity of betulinic acid and lupeol has not been reported. The four isolated compounds were tested for activity against several fungal (Candida albicans, C. spicata, C. guillermondi, Aspergillus fumigatus, Sporothrix shenckii, Cryptococcus neoformans and microsporaum canis) and bacterial (Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa) species. Ursolic acid and hydroxyursolic acid were the most active with MIC values. Hydroxyursolic acid resulted in an MIC value as low as 8 µg/ml against M. canis. A. fumigatus was the most resistant microorganism while M. canis and S. schenckii were the most sensitive. C. albicans was moderately sensitive to the compounds with MIC values ranging from 16 µg/ml for betulinic acid to over 250 µg/ml for lupeol. Compounds isolated in sufficient quantities, namely, lupeol and betulinic acid, were investigated for cytotoxicity against Vero cells. It appeared that lupeol was less toxic than betulinic acid, with LC50 values of 89.5 and 10.9 µg/ml, respectively. The cytotoxicity of betulinic acid was comparable to that induced by the positive control, berberine with an LC50 of 10 µg/ml. Lupeol was the least active of the isolated compounds. Betulinic acid and lupeol, together with the water and acetone extracts were tested in an in vivo rat model to determine antifungal and wound healing activities. The rats were immunocompromised prior to the surgical and treatment procedures. Treatments with any of the formulations did not affect wound healing activity. The rate of wound healing was comparable to both the positive (amphotericin B) and negative (cream only) controls. It was however difficult to judge and score antifungal activity. The model developed to evaluate skin infections will have to be improved to allow for testing for anti-<i.Candida activity in vivo. Some antifungal compounds, such as azoles, are known to also have anthelminthic activity. The isolated compounds, which had antifungal activity, were tested for anthelminthic activity against both parasitic and free-living nematodes. Furthermore, other publications demonstrated that betulinic acid had anthelminthic activity against C. elegans. Lupeol, ursolic acid and betulinic acid, together with the DCM and acetone extracts were investigated for anthelminthic activity against both free living and parasitic nematodes. The acetone and dichloromethane extracts were active against all nematodes to concentrations as low as 160 µg/ml. Betulinic acid and lupeol were active against the parasitic nematodes at high concentrations of 1000 and 200 µg/ml. All compounds were active against the free-living Caenorhabditis elegans with concentrations as low as 8 ìg/ml. Betulinic acid was less active than lupeol and ursolic acid against C. elegans. The acetone and dichloromethane extracts were also active against C. elegans with a concentration of 0.31 mg/ml resulting in almost 80% inhibition of larval motility. It would appear that the anthelminthic activity against both parasitic and free-living nematodes occurred at high concentrations of the compounds or extracts. Extracts of various medicinal plant species may provide the solutions to ill-health of small ruminants caused by parasitic nematodes in poor communities of southern Africa. The extracts of Curtisia dentata and isolated compounds have anti-Candida activity in vitro. Their usage is hampered by associated toxicity. The cytotoxicity of the compounds and extracts was only demonstrated with Vero cells (monkey line). Experiments with several human cell lines may indicate the safety of these compound and extracts when used as treatment against Candida infections. No toxic effects were noted when extracts and isolated compounds were tested in an animal experiment indicating that extracts may be safe in a topical application. The extract from 1 g of leaf material can be diluted to more than a litre and still inhibit the growth of C. albicans. / Thesis (PhD)--University of Pretoria, 2007. / Paraclinical Sciences / unrestricted

Objetivo: Evaluar in vitro la actividad fungistática y fungicida del extracto metanólico de Minthostachys Mollis (Muña) sobre cepas de Candida albicans. Materiales y Métodos: Se realizaron extractos metanólicos de las hojas, tallos y raíces de Minthostachys mollis. La actividad fungistática de los extractos frente a cepas de Candida albicans fue evaluado por medio de la técnica de difusión en agar. La concentración mínima inhibitoria (CMI) del extracto se determinó por el método de microdilución y la citotoxicidad usando la línea celular MDCK. Resultados: El extracto de hojas y tallo de Minthostachys mollis mostró mayor actividad fungistático frente a Candida albicans, observandose halos de inhibición de 47.72±6.67mm y 46.58±6.42mm respectivamente, no encontrando diferencia estadísticamente significativa entre ambos extractos. La CMI fue de 46.87mg/ml, 93.75mg/ml y 1500mg/ml para hojas, tallos y raíces respectivamente. Conclusiones: Se demostró que el extracto metanólico de Minthostachys mollis tienen actividad fungistática y fungicida contra cepas de Candida albicans. Ninguno de los extractos resultó ser tóxico sobre líneas celulares. / Objective: to evaluate in vitro the fungistatic and fungicidal activity of the methanolic extract of Minthostachys Mollis (Muña) on strains of Candida albicans. Methods: Three in vitro methanolic extracts of the leaves, stems and roots of Minthostachys mollis were made. The fungistatic activity of the extracts against Candida albicans strains was evaluated by means of the agar diffusion technique. Minimun inhibitory concentration (MIC) was determined by the microdilution method and cytotoxicity using the MDCK cell line. Results: The extracts that obtained the greatest fungistatic activity at 24 hours were those of leaves and stems against Candida albicans, halos of 47.72 ± 6.67mm and 46.58 ± 6.42mm respectively were obtained, finding no statistically significant difference. The MIC for leaves was 46.87mg / ml, for stems was 93.75mg / ml and 1500mg / ml for roots. Conclusions: It was demonstrated that the methanolic extracts of Minthostachys mollis have fungistatic and fungicidal activity against strains of Candida albicans. None of the extracts turned out to be toxic on cell lines at low concentrations. / Tesis

Glucans are (1→3)-β-linked linear and branched polymers containing anhydroglucose repeat units. They comprise a major portion of the cell wall of saprophytic and pathogenic fungi. Glucans activate a wide range of innate immune responses. They are also released from the fungal cell wall as exopolymers into the blood of patients with fungal infections. Extensive studies have been done on glucans isolated from saprophytic fungi, such as Saccharomyces cerevisiae; however, much less is known about the glucans produced by the polymorphic fungal pathogen Candida albicans. We have undertaken an extensive structural characterization and comparison of glucans isolated from C. albicans blastospores and hyphae using high-resolution, solution-state proton nuclear magnetic resonance spectroscopy (NMR). In addition, we developed a simple and straightforward method for the production of Candida hyphae that resulted in gram quantities of hyphal mass. Also, we compared and contrasted the Candida glucans isolated by two different protocols with those isolated from S. cerevisiae. Isolation protocols provide high purity glucans with source-based structural differences. Structural details provided by this NMR analysis included the degree of polymerization, molecular weight, degree and type of branching, and structural composition. We observed that Candida glucans, derived from blastospores or hyphae, are different compared to those isolated from S. cerevisiae with regard to side-chain branching along the backbone and at the reducing terminus. These structural details are an important prerequisite for biomedical studies on the interaction of isolated fungal cell wall glucans with the innate immune system.

Background: Candida albicans is an opportunistic fungal pathogen that induces strong proinflammatory responses, such as IL-1β production. Much less is known about the induction of immune modulatory cytokines, such as the IL-1 receptor antagonist (IL-1Ra) that is the main natural antagonist of IL-1, by C. albicans. Methods: Peripheral blood mononuclear cells (PBMC) of healthy individuals were stimulated with C. albicans and different components of the fungal cell wall. The role of pathogen recognition receptors (PRRs) for the induction of IL-1β and IL-1Ra was investigated by using specific blockers or in PBMC from Dectin-1 deficient patients. Results: C. albicans induced a strong IL-1Ra response, and this induction was primarily induced by the cell-wall component β-glucan. Blocking IL-1Ra significantly increased C. albicans β-glucan hyphae induced IL-1β and IL-6 production. Surprisingly, blocking the β-glucan receptor Dectin-1 or the downstream Syk or Raf-1 pathways only marginally reduced C. albicans-induced IL-1Ra production, while blocking of the complement receptor 3 (CR3), TLR2 or TLR4 had no effect. In line with this, blocking MAP kinases had little effect on Candida-induced IL-1Ra production. PBMC isolated from Dectin-1 deficient patients produced normal IL-1Ra amounts in response to C. albicans stimulation. Interestingly, the IL-1Ra synthesis induced by β-glucan was blocked by inhibitors of the Akt/PI3. K pathway. Conclusions: β-glucan of C. albicans induces a strong IL-1Ra response, which is independent of the β-glucan receptors dectin-1 and CR3. These data strongly argue for the existence of an unknown β-glucan receptor that specifically induces an Akt/PI3. K-dependent anti-inflammatory IL-1Ra response upon recognition of C. albicans.