Cytokines released from blood monocytes and expressed in mucocutaneous lesions of patients with paracoccidioidomycosis evaluated before and during trimethoprim-sulfamethoxazole treatment

Parise‐Fortes, Maria Rita; Marques, Sílvio Alencar; Soares, Ana Flávia; Kurokawa, Cilmery Suemi; Marques, Mea; Peraçoli, Maria Terezinha Serrão

doi:10.1111/j.1365-2133.2006.07161.x

Cited by 35 publications

(39 citation statements)

References 38 publications

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“…6,17 Experimental and human studies support the hypothesis that PCM granuloma can represent a specific immune response of the host against the fungus. 18 The evolution of the granuloma is related to the host immune response to the components of the cell wall expressed by the fungus. 19 Epithelioid granulomas, obtained from skin or mucosal biopsies of PCM patients, are composed of a central cluster of HLA-DR+ cells, represented by macrophages and epithelioid cells surrounded by a peripheral mantle of Tcells, with the predominance of a CD4+ population.…”

Section: Histological Aspects Of Skin Lesionsmentioning

confidence: 99%

“…20 Therefore, macrophages and T-lymphocytes assume central importance in the morphogenesis of the inflammatory process, and the synergistic action of these cells is important in granuloma formation and modulation through the production of cytokines and other mediators at the inflammatory site. 14,18,21 Morphology of the granulomatous reaction in PCM based on the pattern of immunological response can be represented by setting the two antagonistic poles. In subjects with preserved cellular immune response, compact, well-defined, sometimes confluent epithelioid granulomas can be observed, with few fungi and localized benign infection.…”

Section: Histological Aspects Of Skin Lesionsmentioning

confidence: 99%

“…27,28 During the course of the infection, CD4 Th1 lymphocytes synthesize cytokines such as IFN-γ, TNF-a and IL-12 that protect the host by preventing the spread of the fungus. 14,18,27,38 TNF-α acts on macrophage function in human and experimental PCM modulating and amplifying the immune response, promoting a granulomatous reaction and fungicidal activity mediated by macrophages. 27,39 The absence of this cytokine results in the impairment of defense mechanisms associated with the inability to develop granulomatous reactions, which are effective to contain fungal multiplication.…”

Section: Immunopathogenesis Of Pcmmentioning

confidence: 99%

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Imunologia da paracoccidioidomicose

Fortes¹,

Miot

Kurokawa³

et al. 2011

An. Bras. Dermatol.

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Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, among immunecompetent patients. It's caused by the dimorphic fungus Paracoccidioiddes brasiliensis. Investigations regarding its immunopathogenesis are very important in the understanding of aspects related to natural history, as the protective immunity, and the relationship between host and parasite; also favoring the knowledge about clinical patterns and the elaboration of therapeutic strategies. The disease clinical polymorphism depends, at least, of the immune response profile according to the tissue and blood released citokynes, resulting in tissue damage. Keywords: Allergy and immunology; Cytokines; Paracoccidioides; Paracoccidioidomycosis Resumo: Paracoccidioidomicose é a mais prevalente micose sistêmica na América Latina, em pacientes imunocompetentes, sendo causada pelo fungo dimórfico Paracoccidioiddes brasiliensis. O estudo da sua imunopatogênese é importante na compreensão de aspectos relacionados à história natural, como a imunidade protetora, e à relação entre hospedeiro e parasita, favorecendo o entendimento clínico e a elaboração de estratégias terapêuticas. O polimorfismo clínico da doença depende, em última análise, do perfil de resposta imune que prevalece expresso pelo padrão de citocinas teciduais e circulantes, além da qualidade da resposta imune desencadeada, que levam ao dano tecidual.

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Section: Histological Aspects Of Skin Lesionsmentioning

confidence: 99%

Section: Histological Aspects Of Skin Lesionsmentioning

confidence: 99%

Section: Immunopathogenesis Of Pcmmentioning

confidence: 99%

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Imunologia da paracoccidioidomicose

Fortes¹,

Miot

Kurokawa³

et al. 2011

An. Bras. Dermatol.

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“…Previous morphologic studies of histopathological lesions in human and experimental models of paracoccidioidomycosis found that granulomas consist of accumulated macrophages, epithelioid cells and Pb18 yeast cells of various sizes and sporulation inside MGC (Peraçoli et al 1982, Montenegro & Franco 1994, Parise-Fortes et al 2006. These MGCs may be formed by the macrophage fusion around the fungus that secretes several antigens and can chronically stimulate these cells.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical manifestations of paracoccidioidomycosis are a chronic epithelioid granulomatous disease (Montenegro & Franco 1994) and an inflammatory response induced by the fungus that is supposed to prevent the fungus dissemination (Iabuki & Montenegro 1979, Franco et al 1993. In some histopathology studies of paracoccidioidomycosis in patients and experimentally infected animals, granulomatous lesions with MGC containing fungal cells were present, which suggests that MGC have a role in the fungus-killing process (Parise-Fortes et al 2006). The specific role of MGC in inflammatory infection is not known; however, Enelow et al (1992b) suggest that monocyte cultures stimulated with interleukin (IL)-3 and IFN-γ generate MGC with enhanced candidacidal activity.…”

mentioning

confidence: 99%

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

Bannwart

Nakaira-Takahagi

Peraçoli

2011

Mem. Inst. Oswaldo Cruz

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Multinucleated giant cells (MGC) are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF) in association with other cytokines such as interferon-gamma (IFN-γ), tumour necrosis factor-alpha, interleukin (IL)-10 or transforming growth factor beta (TGF-β1) on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg). The generation of MGC was determined by fusion index (FI) and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18). The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18

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Paracoccidioidomycosis

2005

The Pocket Guide to Fungal Infection

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RESUMENLa paracoccidioidomicosis es una de las micosis profundas más prevalentes en América Latina, causada por el hongo dimófico Paracoccidioides brasiliensis. La enfermedad presenta gran variabilidad clínica y se divide en dos formas de presentación. La forma aguda, que es la menos frecuente (3%-5% de los casos). Y la crónica, la más frecuente (>90% de los casos), que afecta principalmente a hombres mayores de 20-30 años. El diagnóstico se basa en la clínica, visualización microscópica de elementos fúngicos sugestivos de P. brasiliensis, cultivo del hongo de especímenes clínicos, pruebas serológicas, y otros exámenes como rayos X/tomografía axial computarizada (TAC) de acuerdo con la forma y presentación clínica. Cuando se confirma el diagnóstico, todos los pacientes deben recibir tratamiento. Los más usados son el itraconazol y el trimetropim/sulfametoxazol (TMP/ SMX). La anfotericina B se reserva para casos más severos. Las tasas de recaídas son poco frecuentes en aquellos pacientes que reciben un tratamiento completo y adecuado. Sin embargo, estas aumentan si se trata de pacientes inmunocomprometidos o aquellos que suspenden el tratamiento antes de cumplir con los criterios de curación. Es importante realizar un diagnóstico oportuno para evitar las secuelas producidas por la enfermedad, las cuales son más comunes en los pacientes con paracoccidioidomicosis crónica. Palabras clave: micosis; paracoccidioidomicosis; diagnóstico diferencial. ABSTRACTParacoccidioidomycosis is one of the most prevalent systemic mycoses in Latin America. Caused by the dimorphic fungus Paracoccidioides brasiliensis, the disease may have a broad clinical spectrum, and is divided into two forms: the acute form, the least frequent (3%-5% of cases), and the chronic form, the most common (>90% of cases), which primarily affects men aged 20-30 years. The diagnosis is based on clinical presentation, microscopic visualization of the fungus suggestive of P. brasiliensis, culture of the fungus, serology, and other tests, such as X-ray or CT scan, depending on the clinical presentation. Upon diagnosis, all patients must receive treatment. The most common treatments are itraconazole and trimethoprim/sulfamethoxazole; amphotericin B is reserved for severe cases. Relapse rates are infrequent in those who receive the entire treatment. However, they may increase in patients who are immunocompromised or those who stop the treatment before meeting the cure criteria. Developments of sequelae are more common in the chronic form. Thus, early diagnosis is important in order to prevent disabling sequelae caused by the disease.

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Cytokines released from blood monocytes and expressed in mucocutaneous lesions of patients with paracoccidioidomycosis evaluated before and during trimethoprim-sulfamethoxazole treatment

Abstract: Trimethoprim-sulfamethoxazole therapy was effective in decreasing fungal load in the lesions, allowing patient immune response to control the infection leading to the healing of the lesions.

Cited by 35 publications

References 38 publications

Imunologia da paracoccidioidomicose

Imunologia da paracoccidioidomicose

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

Paracoccidioidomycosis

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