Paracoccidioidomycosis

Benard, Gil; Franco, Marcello

doi:10.1002/9780470688618.taw0155

Cited by 3 publications

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“…PCM has a multiplicity of clinical presentations, from cutaneous to systemic forms, and can attack various tissues, especially the lungs (Benard & Franco, 2007). Oral mucosal lesions are commonly multiple, with a granular, mulberry-like surface and microulcerations, and microscopically are observed as a granulomatous inflammatory reaction and pseudoepitheliomatous hyperplasia that can be mistaken as neoplastic (Kaminagakura et al, 2006;Moscardi-Bacchi et al, 1989;Scully & de Almeida, 1992), which can be a problem clinically as the oral lesions of PCM closely resemble carcinoma (Kaminagakura et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Differential gene expression analysis of Paracoccidioides brasiliensis during keratinocyte infection

Silva

Matsumoto

Braz

et al. 2011

Journal of Medical Microbiology

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Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, one of the most important systemic fungal diseases in Latin America. This initiates in lung tissue and can subsequently disseminate to other tissues. Clinical manifestations range from localized forms to disseminated disease that can progress to lethality, probably depending on the relationships among the virulence of the fungus, the immune response and the ability to interact with the surface structures and invade epithelial cells and mononuclear cells of the host. It is generally regarded as a multifocal disease, with oral lesions as the prominent feature. The aim of this study was to evaluate P. brasiliensis yeast infection in normal oral keratinocytes (NOKs). The differential expression of mRNAs and proteins was also determined when the fungus was placed in contact with the cell in order to characterize differentially expressed genes and proteins during P. brasiliensis infection. After contact with NOKs, the fungus appeared to induce alterations in the cells, which showed cellular extensions and cavitations, probably resulting from changes in the actin cytoskeleton seen at 5 and 8 h after infection. Levels of protein expression were higher after reisolation of the fungus from infected NOK culture compared with culture of the fungus in medium. The analysis identified transcripts related to 19 proteins involved in different biological processes. Transcripts were found with multiple functions including induction of cytokines, protein metabolism, alternative carbon metabolism, zinc transport and the stress response during contact with NOKs. The proteins found suggested that the yeast was in a stress situation, as indicated by the presence of RDS1. Nevertheless, the yeast seemed to be proliferating and metabolically active, as shown by the presence of a proteasome, short-chain acetylator, glucosamine-6-phosphate isomerase and ADP/ATP carrier transcripts. Additionally, metabolic pathways may have been activated in order to eliminate toxic substances from the cell as a zinc transporter was detected, which is a potential target for the development of future drugs. INTRODUCTIONParacoccidioides brasiliensis is a thermodimorphic pathogenic fungus, the aetiological agent of paracoccidioidomycosis (PCM), an endemic disease geographically limited to Latin America and one of the most prevalent human deep systemic mycoses found in Brazil, Colombia and Venezuela (San-Blas et al., 2002). The transition from mycelium at 25 u C to yeast at 37 u C is essential for P. brasiliensis to establish the disease (Franco et al., 1997). P. brasiliensis may be inhaled and, once in the lungs, the fungus initiates a process of morphological transition into the pathogenic yeast form (San-Blas et al., 2002).PCM has a multiplicity of clinical presentations, from cutaneous to systemic forms, and can attack various tissues, especially the lungs (Benard & Franco, 2007). Oral mucosal lesions are commonly multiple, with a granular, mulberry-like surface and microulcerations, and ...

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Section: Introductionmentioning

confidence: 99%

Differential gene expression analysis of Paracoccidioides brasiliensis during keratinocyte infection

Silva

Matsumoto

Braz

et al. 2011

Journal of Medical Microbiology

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“…The initial chest CT scan did not rule out paracoccidioidomycosis ( 7 ). However, seronegative rheumatoid arthritis was diagnosed and treated.…”

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“…A new CT scan of the chest indicated cystic bronchiectasis, bronchial wall thickening, and adjacent areas of consolidation. Microscopic examination of thumb secretion and sputum samples by using 10% potassium hydroxide revealed the characteristic pilot’s wheel appearance of Paracoccidioides brasiliensis, showing multiple-budding yeast cells with well-defined refringent double walls ( 7 ) ( Figure , panel C). Grocott-Gomori stain of a skin biopsy specimen demonstrated yeast with the same microscopic features ( 7 ).…”

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confidence: 99%

Carpal Tunnel Syndrome with Paracoccidioidomycosis

Glehn¹,

Damasceno²,

Miotto³

et al. 2012

Emerg. Infect. Dis.

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“…Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America, with Brazil contributing the highest number of cases (1). Host resistance to Paracoccidioides brasiliensis relies on cell-mediated immune response, predominantly of the Th-l phenotype, and by the ability of the T cells to proliferate in response to fungal antigens and generate effector T cells (1).…”

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confidence: 99%

“…Host resistance to Paracoccidioides brasiliensis relies on cell-mediated immune response, predominantly of the Th-l phenotype, and by the ability of the T cells to proliferate in response to fungal antigens and generate effector T cells (1). Several researchers have shown that T cells from patients with disseminated PCM have decreased proliferative responses and production of Th-1 cytokines, such as interleukin-2 (IL-2) and gamma interferon, in response to P. brasiliensis antigens, while individuals with cured, inactive disease exhibit high response levels (2).…”

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Altered Ex Vivo Expression of Caspase 8, Caspase 9, and Bcl-2 Is Associated with T-Cell Hyporeactivity in Patients with Paracoccidioidomycosis

Cacere

Mendes-Giannini

Valle

et al. 2009

Clin Vaccine Immunol

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To better understand the T-cell hyporesponsiveness of patients with paracoccidioidomycosis, we tested the hypothesis that the T cells were committed to apoptosis. We show here that T cells of patients with paracoccidioidomycosis overexpress caspase 9 and caspase 8 but express low Bcl-2 levels and that interleukin-2 was unable to revert the hyporesponsiveness. These data suggest that the T cells would in vivo be driven to a tolerant state and apoptosis.Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America, with Brazil contributing the highest number of cases (1). Host resistance to Paracoccidioides brasiliensis relies on cell-mediated immune response, predominantly of the Th-l phenotype, and by the ability of the T cells to proliferate in response to fungal antigens and generate effector T cells (1). Several researchers have shown that T cells from patients with disseminated PCM have decreased proliferative responses and production of Th-1 cytokines, such as interleukin-2 (IL-2) and gamma interferon, in response to P. brasiliensis antigens, while individuals with cured, inactive disease exhibit high response levels (2). Thus, this defect likely underlies the failure of the host immune responses in controlling the infection (2, 14). The mechanisms responsible for this T-cell hyporesponsiveness are still poorly understood. In previous studies, we detected ex vivo overexpression of several costimulatory molecules in T cells and monocytes from patients with PCM, with most of these molecules downregulating T-cell activation, suggesting that these cells had been activated in vivo (16). In an attempt to revert this in vitro hyporesponsiveness, we carried out experiments in which engagement of these molecules was blocked with monoclonal antibodies specific to each of the molecules. However, this strategy failed to restore the proliferative responses (16).Thus, to gain improved insight into this T-cell hyporesponsiveness, we tested in the present study the possibility that the T cells were committed to ex vivo apoptosis by measuring the intracellular levels of proteins involved with the apoptosis pathways, such as caspase 9, caspase 8, and Bcl-2, as well as the potential of IL-2 in rescuing this hyporesponsiveness. Caspase 9 and Bcl-2 are associated mainly with the intrinsic pathway, which is typically triggered by deprivation of growth factors, such as IL-2 (12). A lack or removal of growth factors leads to decreased expression of some antiapoptotic molecules (e.g., Bcl-2) and activation of other proapoptotic molecules (e.g., caspase 9), culminating in caspase 3 activation and cell death. The extrinsic pathway depends on the Fas/CD95/APO-1 pathway, which activates caspase 8 and caspase 3, bypassing the mitochondria (12). This pathway is preferentially triggered by repetitive antigen stimulation or by exposure to high antigen loads (11). The ex vivo expression of these proteins was quantified by flow cytometry (EPICS-XL; Beckman-Coulter) with cells isolated by a Ficoll-Hypaque gradient (Sigm...

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Paracoccidioidomycosis

Cited by 3 publications

References 97 publications

Differential gene expression analysis of Paracoccidioides brasiliensis during keratinocyte infection

Differential gene expression analysis of Paracoccidioides brasiliensis during keratinocyte infection

Carpal Tunnel Syndrome with Paracoccidioidomycosis

Altered Ex Vivo Expression of Caspase 8, Caspase 9, and Bcl-2 Is Associated with T-Cell Hyporeactivity in Patients with Paracoccidioidomycosis

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