Paracoccidioidomycosis in patients with Lymphoma and review of published literature

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

DNA damage in BALB/c mice infected with Lacazia loboi and its relation to nutritional status

Background: Jorge Lobo's disease, also known as lacaziosis, is a cutaneous-subcutaneous mycosis with chronic evolution. It is caused by the fungus Lacazia loboi. Herein we report a study that relates the genotoxicity caused by L. loboi in isogenic mice with nutritional status, through a normal or restricted diet.Methods: DNA damage was assessed in the peripheral blood by the comet assay (tail intensity).Results: The results for leukocytes showed increases in the mean tail intensity in mice under dietary restriction, in infected mice under dietary restriction and in infected mice ingesting a normal diet.Conclusion: These results indicate that dietary restriction and L. loboi infection may increase DNA damage levels in mice, as detected by the comet assay.

Paracoccidioides brasiliensis interferes on dendritic cells maturation by inhibiting PGE(2) production

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

Importance of adhesins in virulence of Paracoccidioides spp.

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

Neutrophil extracellular traps identification in tegumentary lesions of patients with paracoccidioidomycosis and different patterns of NETs generation in vitro

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

Participation of dectin-1 receptor on NETs release against Paracoccidioides brasiliensis: role on extracellular killing

Paracoccidioides brasiliensis is a dimorphic fungus from the Paracoccidioides genus, which is the causative agent of paracoccidioidomycosis, a chronic, subacute or acute mycosis, with visceral and cutaneous involvement. This disease that is acquired through inhalation primarily attacks the lungs but, can spread to other organs. Phagocytic cells as neutrophils play an important role during innate immune response against this fungus, but studies on antifungal activities of these cells are scarce. In addition to their ability to eliminate pathogens by phagocytosis and antimicrobial secretions, neutrophils can trap and kill microorganisms by release of extracellular structures composed by DNA and antimicrobial proteins, called neutrophil extracellular traps (NETs). Here, we provide evidence that P. brasiliensis virulent strain (P. brasiliensis 18) induces NETs release. These structures were well evidenced by scanning electron microscopy, and specific NETs compounds such as histone, elastase and DNA were shown by confocal microscopy. In addition, we have shown that dectin-1 receptor is the main PRR to which fungus binds to induce NETS release. Fungi were ensnared by NETs, denoting the role of these structures in confining the fungus, avoiding dissemination. NETs were also shown to be involved in fungus killing, since fungicidal activity detected before and mainly after neutrophils activation with TNF-α, IFN-γ and GM-CSF was significantly inhibited by cocultures treatment with DNAse.

Estudo dos mecanismos de resistência e virulência de isolados de Cryptococcus neoformans e Cryptococcus gattii e quantificação de genes de bomba de efluxo pós tratamento com Galatos de Alquila

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Funcionalidade das proteínas EF-Tu e 14-3-3 na virulência de Paracoccidioides brasiliensis

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

Chromosome aberrations in lymphocyte cultures from paracoccidioidomycosis patients

Blood cell lymphocyte chromosomes from untreated (UT) and clinically-cured (CC) patients with paracoccidioidomycosis and from healthy (control) people (CO) were studied. The frequency of aneuploid cells in the UT patients was higher than in the CC and CO individuals. The frequency of metaphase cells with premature centromere division was significantly higher in the UT than in the CC and CO group. No structural aberration and no statistically significant difference in the frequency of polyploidy was observed in the three groups studied. Our findings are indicative of an aneugenic (aneuploidy-inducing) action of infection by Paracoccidioides brasiliensis.

Positividade do imunomarcador FOXP3 em células T reguladoras em lesões de micose fungoide em fases clínicas iniciais e em dermatoses inflamatórias como fator auxiliar para o diagnóstico diferencial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Manifestación bucal de paracoccidiodomicosis asociada a aspergilosis: presentación de caso

Paracoccidioidomycosis and aspergillosis are, respectively, mycosis caused by Paracoccidioides brasiliensis and Aspergillus fumigatus fungi, which, most frequently, attack the lungs and later spread to other body regions. The association between both mycosis is rare in patients that do not present immunosuppression. A 49-year-old man presented with oral lesion, besides lesions on palatum, retromolar and oropharyngeal regions. Histopathological and microbiological exams confirmed the diagnosis of paracoccidioidomycosis associated to aspergillosis. Historically, fungi have been considered as the cause of relatively important infections, but, in the last years, a significant increase of diseases caused by fungi is evidenced. The recognition of the etiological agent in culture is important for the suitable treatment, once these fungi can cause irreversible damages or even death. The purpose of this study was to demonstrate, through the case of a patient who presented both mycosis associated, the need of complementary exams for the diagnosis of oral diseases, when routine laboratorial exams indicate the presence of another disease associated.

Análise retrospectiva de 61 casos de paracoccidioidomicose diagnosticados na Faculdade de Odontologia de Araçatuba/ UNESP

Paracoccidioidomycosis is a systemic mycosis which requires prolonged treatment. It is highest prevalence in Latin America, with different endemic areas in Brazil. In this study the aim was to characterize clients suffering from mucocutaneous paracoccidioidomycosis by analysis of histopathological examinations of 61 adult patients diagnosed with mucocutaneous paracoccidioidomycosis treated at the Dental School of Araçatuba, from January 1989 to December 2004. It was observed that the disease occurred in 91.81% (56) men and 8.19% (5) women, more prevalent (78.68%) in whites, aged 40 to 59 years (62.9%) and the profession linked to agriculture in 17 patients (27.86%). All patients had oral manifestations, in multiple sites, but it was most prevalent in the oral mucosa (31.42%) and alveolar ridge (17.14%). The dentist as an integral member of the health services, must know the clinical manifestations of paracoccidioidomycosis to achieve early diagnosis and thereby to improve the quality of life of patients.

Novas alternativas terapêuticas para o tratamento da Criptococose: análogos de Resveratrol e microRNAs

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito imunomodulatório e controle da infecção fúngica do extrato de alho (Allium sativum L.) em modelo murino de esporotricose

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Anti-CD25 Treatment Depletes Treg Cells and Decreases Disease Severity in Susceptible and Resistant Mice Infected with Paracoccidioides brasiliensis

Regulatory T (Treg) cells are fundamental in the control of immunity and excessive tissue pathology. In paracoccidioidomycosis, an endemic mycosis of Latin America, the immunoregulatory mechanisms that control the progressive and regressive forms of this infection are poorly known. Due to its modulatory activity on Treg cells, we investigated the effects of anti-CD25 treatment over the course of pulmonary infection in resistant (A/J) and susceptible (B10.A) mice infected with Paracoccidioides brasiliensis. We verified that the resistant A/J mice developed higher numbers and more potent Treg cells than susceptible B10.A mice. Compared to B10.A cells, the CD4(+)CD25(+)Foxp3(+) Treg cells of A/J mice expressed higher levels of CD25, CTLA4, GITR, Foxp3, LAP and intracellular IL-10 and TGF-beta. In both resistant and susceptible mice, anti-CD25 treatment decreased the CD4(+)CD25(+)Foxp3(+) Treg cell number, impaired indoleamine 2,3-dioxygenase expression and resulted in decreased fungal loads in the lungs, liver and spleen. In A/J mice, anti-CD25 treatment led to an early increase in T cell immunity, demonstrated by the augmented influx of activated CD4(+) and CD8(+) T cells, macrophages and dendritic cells to the lungs. At a later phase, the mild infection was associated with decreased inflammatory reactions and increased Th1/Th2/Th17 cytokine production. In B10.A mice, anti-CD25 treatment did not alter the inflammatory reactions but increased the fungicidal mechanisms and late secretion of Th1/Th2/Th17 cytokines. Importantly, in both mouse strains, the early depletion of CD25(+) cells resulted in less severe tissue pathology and abolished the enhanced mortality observed in susceptible mice. In conclusion, this study is the first to demonstrate that anti-CD25 treatment is beneficial to the progressive and regressive forms of paracoccidioidomycosis, potentially due to the anti-CD25-mediated reduction of Treg cells, as these cells have suppressive effects on the early T cell response in resistant mice and the clearance mechanisms of fungal cells in susceptible mice.