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2.
Med Mycol ; 53(1): 69-89, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25362733

RESUMEN

Mycoses are gaining increasing attention in modern medicine because of the increase in diseases associated with opportunistic fungal infections. Despite the recognized role of the immune system in the control of fungal infections, no antifungal vaccines are currently licensed for use in humans. However, numerous vaccine candidates are being developed in many laboratories, as proof of the renewed interest in integrating or replacing chemotherapy with vaccines to reduce antibiotic use and consequently limit drug resistance and toxicity. In the effort to use safer and simpler fungal antigens for vaccinations, adjuvants have become relevant as immunostimulators to elicit successful protective immune responses. To address the relevant role of adjuvants as determinants in the balance of vaccine efficacy and safety, an updated and critical review of the adjuvants used in preclinical antifungal vaccines is presented, and prospective trends are addressed. Selected recent papers and other historically relevant and innovative strategies using adjuvants in experimental fungal vaccines are highlighted.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Sistemas de Liberación de Medicamentos , Vacunas Fúngicas/inmunología , Micosis/prevención & control , Descubrimiento de Drogas/tendencias , Vacunas Fúngicas/administración & dosificación , Humanos , Micosis/inmunología
3.
Immunol Invest ; 43(4): 370-90, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24484374

RESUMEN

Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 in the recognition of S. schenckii and in the subsequent immune response. Therefore, the aim of this study was to evaluate the involvement of TLR-2 in the immune response induced by S. schenckii. C57BL/6 mice (WT) and C57BL/6 TLR-2 knockout (TLR-2-/-) were used to evaluate, over a period of 10 weeks of sporotrichotic infection, the influence of TLR-2 over macrophages production of IL-1ß, IL-12 and TNF-α, their stimulation level by NO release and the production of IFN -γ, IL-6, IL-17 and TGF-ß by spleen cells. The results showed that the production of pro-inflammatory mediators and NO, TLR-2 interference is striking, since its absence completely inhibited it. IL-17 production was independent of TLR-2. The absence of Th1 response in TLR2-/- animals was concomitant with IL-17 production. Therefore, it can be suggested that TLR-2 absence interferes with the course of the infection induced by the fungus S. schenckii.


Asunto(s)
Sporothrix/inmunología , Esporotricosis/inmunología , Esporotricosis/metabolismo , Receptor Toll-Like 2/metabolismo , Animales , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Femenino , Humanos , Interleucina-12/biosíntesis , Interleucina-1beta/biosíntesis , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Noqueados , Óxido Nítrico/metabolismo , Tamaño de los Órganos , Bazo/metabolismo , Bazo/patología , Receptor Toll-Like 2/genética , Factor de Necrosis Tumoral alfa/biosíntesis
4.
Immunol Invest ; 42(1): 36-48, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23231043

RESUMEN

Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2(-/-) animals. The results showed that TLR-2(-/-) animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2(-/-). The absence of TLR-2 led to lower production of the cytokines TNF-α, IL-1ß, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii.


Asunto(s)
Antígenos Fúngicos/inmunología , Macrófagos/inmunología , Sporothrix/inmunología , Esporotricosis/inmunología , Receptor Toll-Like 2/inmunología , Animales , Células Cultivadas , Citocinas/metabolismo , Femenino , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Macrófagos/microbiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fagocitosis/inmunología , Receptor Toll-Like 2/genética
5.
Z Naturforsch C J Biosci ; 68(7-8): 293-301, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24066514

RESUMEN

Palladium(II) complexes are an important class of cyclopalladated compounds that play a pivotal role in various pharmaceutical applications. Here, we investigated the antitumour, anti-inflammatory, and mutagenic effects of two complexes: [Pd(dmba)(Cl)tu] (1) and [Pd(dmba)(N3)tu] (2) (dmba = N,N-dimethylbenzylamine and tu = thiourea), on Ehrlich ascites tumour (EAT) cells and peritoneal exudate cells (PECs) from mice bearing solid Ehrlich tumour. The cytotoxic effects of the complexes on EAT cells and PECs were assessed using the 3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The effects of the complexes on the immune system were assessed based on the production of nitric oxide (NO) (Griess assay) and tumour necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12), and interleukin-10 (IL-10) (ELISA). Finally the mutagenic activity was assessed by the Ames test using the Salmonella typhimurium strain TA 98. Cisplatin was used as a standard. The IC50 ranges for the growth inhibition of EAT cells and PECs were found to be (72.8 +/- 3.23) microM and (137.65 +/- 0.22) microM for 1 and (39.7 +/- 0.30) microM and (146.51 +/- 2.67) microM for 2, respectively. The production of NO, IL-12, and TNF-alpha, but not IL-10, was induced by both complexes and cisplatin. The complexes showed no mutagenicity in vitro, unlike cisplatin, which was mutagenic in the strain. These results indicate that the complexes are not mutagenic and have potential immunological and antitumour activities. These properties make them promising alternatives to cisplatin.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Carcinoma de Ehrlich/patología , Paladio/farmacología , Animales , Línea Celular Tumoral , Ratones , Óxido Nítrico/metabolismo
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