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MICAFUGIN ENHANCES THE HUMAN IMMUNE RESPONSE AGAINST C. ALBICANS.
Autores:
JOSE PEDRO GUIRAO ABAD
, RUTH SÁNCHEZ-FRESNEDA,
JUAN CARLOS ARGÜELLES ORDOÑEZ
,
MARÍA CONCEPCIÓN MARTÍNEZ-ESPARZA ALVARGONZÁLEZ
,
Grupos de investigación:
[GI/IMIB/C063/2011] Inmunidad innata en la salud y la enfermedad
Comunicación:
Antecedentes:
Echinocandins are antifungal compounds which inhibits the activity of ?glucan synthase thus disrupting cell wall formation and function. Caspofungin and micafungin are members of this family. Several studies have shown that caspofungin is an antifungal drug with an important immunomodulatory role in the response against C. albicans. Sub-lethal doses of this echinocandin are able to unmask cell wall ?-glucans, which are detected by macrophages through Dectin-1, increasing the production of pro-inflammatory cytokines as TNF-?, Il-12, Il-17 and INF-?. However, this behavior has not been studied yet for micafungin. The objective of this work is to analyze the effect of micafungin treatment on C. albicans cells in the immune response of human macrophages.
Métodos:
For that, peritoneal human macrophages were isolated and purified from healthy donors. The SC5314 C. albicans strain was treated with different concentrations of micafungin and the CMI50 were calculated. The effect of micafungin on the expression of ?-glucans in the C. albicans cell wall was studied by flow cytometry. Macrophages were co-cultured in vitro for 4h at ratio 1:5 macrophage:yeast, with SC5314 yeast strain untreated or pre-treated for 1h with micafungin (0.005 µg/ml; 0.01 µg/ml; 0.05 µg/ml). The supernatants was then recovered and the cytokine content was analyzed by ELISA.
Resultados:
Micafungin treatment induces the exposition of ?-glucans on the C. albicans cell wall surface. SC5314 cells pretreated with lethal doses of micafungin (0.05 µg/ml) compared with untreated yeast cells, induced a statistically significant increase in the secretion of the pro-inflammatory and anti-inflammatory cytokines TNF-? and Il-10, respectively in human peritoneal macrophages. This increase was not observed when the yeast cells were pretreated with sub-lethal doses of micafungin (0.005 µg/ml; 0.01 µg/ml). On the other hand, the results found for low IL-17A followed the same tendency observed for TNF-? and IL-10, although were not statistically significant.
Conclusiones:
In conclusion, our results demonstrate that C. albicans micafungin treatment increases its recognition by human macrophages and their consequent activation, reflected by higher cytokine levels, which facilitates the removal of the fungal infection.
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