Effects of propolis from Brazil and Bulgaria on fungicidal activity of macrophages against Paracoccidioides brasiliensis

Paracoccidioidomycosis is the most important systemic mycosis in Latin America. Its etiological agent, Paracoccidoides brasiliensis, affects individuals living in endemic areas through inhalation of airborne conidia or mycelial fragments. The disease may affect different organs and systems, with multiple clinical features, with cell-mediated immunity playing a significant role in host defence. Peritoneal macrophages from BALB/c mice were stimulated with Brazilian or Bulgarian propolis and subsequently challenged with P, brasiliensis. Data suggest an increase in the fungicidal activity of macrophages by propolis stimulation, independently from its geographic origin, (C) 2002 Elsevier B.V. Ireland Ltd. All rights reserved.

Effect of interleukin-10 on the Paracoccidioides brasiliensis killing by gamma-interferon activated human neutrophils

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Virulence attenuation and phenotypic variation of Paracoccidioides brasiliensis isolates obtained from armadillos and patients

Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis, the most important systemic mycosis in Latin America. The virulence profiles of five isolates of P. brasiliensis were studied in two different moments and correlated with some colonial phenotypic aspects. We observed a significant decrease in the virulence and an intense phenotypic variation in the mycelial colony. The recognition of all ranges of phenotypic and virulence variation of P. brasiliensis, as well as its physiological and genetic basis, will be important for a better comprehension of its pathogenic and epidemiological features.

Cytokine production in experimental paracoccidioidomycosis of murine selected lineages for acute inflammatory response (air)

Paracoccidioidomycosis is a systemic human mycosis caused by Paracoccidioides brasiliensis (P. brasiliensis), an imperfect dimorphic fungus whose conidia are its infective form. Mice genetically selected for maximum (AIRmax) and minimum (AIRmin) acute inflammatory response were used as experimental paracoccidioidomycosis models. The animals were intraperitoneally inoculated with P. brasiliensis (strain 18) and killed 6, 12 and 24 hours or 3, 7 and 14 days after infection. In these periods, fragments from their spleen, liver and lung were removed for evaluation of the infection level by fungal cells, assessment of macrophagic activity by peritoneal and splenic macrophages - through the determination of nitric oxide (NO) concentrations and production of pro- and anti-inflammatory cytokines of lung and spleen homogenate supernatants. In the present study, it was observed that AIRmax lineages presented greater control of the infectious process than the AIRmin ones. Regarding NO production, AIRmax animals produced more metabolites in late periods, what may help control the infectious process. Concerning cytokine production, it was observed that the production of INF-gamma, TNF-alpha, IL-1, IL-6, IL-8 and IL-12 were increased in AIRmax lineages in most analyzed organs and periods, thus contributing to the greater resistance exhibited by such lineages against infection, except for IL-4 and IL-10 that showed decreased production in AIRmax lineage, reproducing its suppressive biological effect. From these results, it was observed that the AIRmax lineage was more effective in controlling the infectious process, with an important involvement of the analyzed cytokines. These findings are probably related to the genetically selected factors involved in the acute inflammatory response.

ROLE of TLR2 and TLR4 on human neutrophil functions against Paracoccidioides brasiliensis

In paracoccidioidomycosis, a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb), studies have focused on the role of neutrophils that are involved in the primary response to the fungus. Neutrophil functions are regulated by pro- and anti-inflammatory cytokines. Molecular mechanisms involved in this process are not fully understood, but there are strong evidences about the involvement of toll-like receptors (TLRs). We aimed at evaluating TLR2 and TLR4 expression on human neutrophils activated by GM-CSF, IL-15, TNF-alpha or IFNgamma and challenged with a virulent strain of P. brasiliensis (Pb18). Moreover, we asked if these receptors have a role on fungicidal activity, H(2)O(2) and IL-6, IL-8, TNFalpha and IL-10 production, by activating and challenging cells. All cytokines increased TLR2 and TLR4 expression. Pb18 also increased TLR2 expression, inducing an additional cytokine effect. on the contrary, it inhibited TLR4 expression. All cytokines increased neutrophil fungicidal activity and H(2)O(2) production; however, this process was not associated with TLR2 or TLR4. Neutrophil activation by GMCSF and TNF-alpha resulted in a significant increase of IL-8 production, while IL-15 and IFN-alpha have no effect. Pb18 also augmented IL-8 expression, inducing an additional effect to that of cytokines. None of the cytokines activated neutrophils by releasing IL-10. This cytokine was only detected after Pb18 challenge. Interestingly, IL-8 and IL-10 production involved TLR2 and mainly TLR4 modulation. The present results suggest that Pb18 interaction with neutrophils through TLR2 and TLR4 with consequent IL-8 and IL-10 production may be considered a pathogenic mechanism in paracoccidioidomycosis.

Paracoccidioides brasiliensis Uses Endogenous and Exogenous Arachidonic Acid for PGE(x) Production

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent deep mycosis in Latin America. Production of eicosanoids during fungal infections plays a critical role on fungal biology as well as on host immune response modulation. The purpose of our study was to assess whether P. brasiliensis strains with different degree of virulence (Pb18, Pb265, Bt79, Pb192) produce prostaglandin E-x (PGE(x)). Moreover, we asked if P. brasiliensis could use exogenous sources of arachidonic acid (AA), as well as metabolic pathways dependent on cyclooxygenase (COX) enzyme, as reported for mammalian cells. A possible association between this prostanoid and fungus viability was also assessed. Our results showed that all strains, independently of their virulence, produce high PGE(x) levels on 4 h culture that were reduced after 8 h. However, in both culture times, higher prostanoid levels were detected after supplementation of medium with exogenous AA. Treatment with indomethacin, a COX inhibitor, induced a reduction on PGEx, as well as in fungus viability. The data provide evidence that P. brasiliensis produces prostaglandin-like molecules by metabolizing either endogenous or exogenous AA. Moreover, the results suggest the involvement of these mediators on fungal viability.

Interleukin-10 but not Transforming Growth Factor beta inhibits murine activated macrophages Paracoccidioides brasiliensis killing: Effect on H2O2 and NO production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Production of leukotriene B4 by Paracoccidioides brasiliensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of TLR2 and TLR4 in Human Neutrophil Functions Against Paracoccidioides brasiliensis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genus Paracoccidioides: Species Recognition and Biogeographic Aspects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Oral Exfoliative Cytology for the Diagnosis of Paracoccidioidomycosis in a Patient with Human Immunodeficiency Virus A Case Report

BackgroundParacoccidioidomycosis is not the most common fungal disease in patients infected with human immunodeficiency virus (HIV), except for endemic regions in Latin America countriesCaseA 33-year-old man with HIV presented with mulberry-like lesions on the palate The diagnosis was made by exfoliative cytology and Papanicolaou staining Microscopic analysis revealed fungal structures with birefringent walls and exosporulation conferring an airplane radial motor appearance, or even bowel-like or goblet-like forms compatible with Paracoccidioides brasiliensisConclusionThis process spares the immunosuppressed patient from under going invasive biopsy procedures (Acta Cytol 2010,54 1127-1129)

Natural antibodies in paracoccidioidomycosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Paracoccidioidomicose em paciente com carcinoma do colo uterino

Os autores relatam caso de paciente do sexo feminino com paracoccidioidomicose, associada a carcinoma do colo uterino estádio IIIB. Paracoccidioidomicose, associada à neoplasia, ocorre entre 0,16% a 14,1% segundo diferentes séries de casos. em casos com neoplasia disseminada a infecção fúngicas pode apresentar comportamento oportunístico

White piedra and pediculosis capitis in the same patient

Piedra branca é micose superficial causada pelo gênero Trichosporon e caracterizada por nódulos aderidos à haste do pelo. Pediculose capitis é causada pelo Pediculus humanus var. capitis pertencente à subordem Anoplura. Enquanto que a pediculose é enfermidade comum, relatos clínicos de piedra branca são raros. Técnicas de biologia molecular identificaram o agente de piedra branca do presente relato como T.inkin. Os autores apresentam associação de ambas as infestações no mesmo paciente para salientar seus aspectos clínicos distintos.

Virulence Factors IN Fungi of Systemic Mycoses

Fatores de virulência em fungos de micoses sistêmicaFungos patogênicos causadores de micoses sistêmicas possuem vários fatores que permitem seu crescimento nas condições adversas oferecidas pelo hospedeiro, propiciando o estabelecimento da relação parasitária e contribuindo no processo de doença. Esses fatores são conhecidos como fatores de virulência auxiliando no desenvolvimento da infecção e interferindo com a patogênese das micoses. O presente trabalho avalia os fatores de virulência em fungos patogênicos como Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum e Paracoccidioides brasiliensis, em relação à termotolerância, dimorfismo, componentes da parede celular ou cápsula, bem como a produção de enzimas. Os fatores de virulência auxiliam na aderência, colonização, disseminação e habilidade do fungo para resistir a ambientes hostis e escapar dos mecanismos da resposta imune do hospedeiro.Tanto os fatores de virulência apresentados por diferentes fungos, como os mecanismos de defesa oferecidos pelo hospedeiro requerem ação e interação de processos complexos, cujo conhecimento permitirá a melhor compreensão da patogenia das micoses sistêmicas.