Participação do receptor toll-like4 na resposta imune durante a esporotricose ecperimental
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Data
2008-11-18
Autores
Sassá, Micheli Fernanda [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Os receptores “toll-like” (TLR) são importantes no reconhecimento de patógenos por um hospedeiro e conseqüentemente para a ativação da resposta imune inata. Evidências clínicas e experimentais mostram que defeitos nesses receptores ou em suas vias de sinalização deixam o hospedeiro suscetível a vários tipos de infecção. Já foi demonstrado que o TLR2 e o TLR4 estão envolvidos no reconhecimento de vários fungos, como Candida albicans, Aspergillus niger, Aspergillus fumigatus e Saccharomyces cerevisiae, entretanto não há informações disponíveis sobre a participação dos TLRs no reconhecimento do Sporothrix schenckii. O S. schenckii é um fungo termodimórfico causador da esporotricose, uma infecção micótica caracterizada pelo comprometimento da pele e tecidos subcutâneos; em algumas ocasiões, como em pacientes imunocomprometidos, pode induzir lesões em órgãos. Os mecanismos de defesa, principalmente a imunidade mediada por células, são importantes na resistência à infecção. O objetivo deste trabalho foi verificar o papel do TLR4 na resposta dos macrófagos ao S. schenckii, empregando camundongos defectivos na expressão de TLR4 (C3H/HeJ) e camundongos controle (C3H/HePas), através da avaliação de mediadores imunológicos produzidos pelas células peritoneais dos camundongos, da expressão de proteínas acessórias ao TLR4 e da avaliação da apoptose destas células durante dez semanas. A produção dos intermediários reativos do oxigênio, determinada através da técnica de redução do vermelho de fenol, revelou que os camundongos defectivos na expressão do TLR4 produziram menores concentrações de H2O2 que os camundongos TLR4 normais. Nestes, as maiores concentrações de H2O2 foram induzidas pela presença do extrato lipídico da fase miceliar do S. schenckii. No entanto, a produção de óxido nítrico (NO) e das citocinas ocorreu...
Toll-like receptors (TLR) are important to pathogen recognition by a host and to the subsequent triggering of an innate immune response. Experimental and clinical evidence show that defects in TLR or in signaling pathways downstream from these receptors render hosts susceptible to various types of infection. TLR2 and TLR4 are involved in recognition of several fungi, such as Candida albicans, Aspergillus niger, Aspergillus fumigatus and Saccharomyces cerevisiae. However, no information is available about TLR recognition of Sporothrix schenckii. S. schenckii is a thermally dimorphic fungus, the causative agent of sporotrichosis, a mycotic infection characterized by frequent involvement of the skin and subcutaneous tissues; occasionally, it may also produce lesions of the internal organs mostly reported among immunocompromised hosts. Immune defense mechanisms, particularly cellmediated immunity have been reported to be important in infection resistance. The aim of this study was to assess the role of TLR4 in the response of macrophages to S. schenckii, using TLR4-deficient mice (C3H/HeJ) and control mice (C3H/HePas), evaluating immunological mediators produced by exudate peritoneal cells, TLR4 accessory protein expression, and apoptosis of these cells over a period of ten weeks. Reactive oxygen intermediates production was determined through phenol red oxidation method and has revealed that TLR4-defective mice produced lower levels of H2O2 than TLR4 normal mice. In these animals, higher H2O2 concentrations were seen when lipid extract obtained from S. schenckii mycelium was used. However, nitric oxide (NO) and cytokine production occurred in higher levels when cells were challenged with lipid extract from S. schenckii yeast cells, which is the morphotype found in the host during infection. NO and cytokines such as IL-1, TNF- and IL-10 production in culture supernatants were also lower... (Complete abstract click electronic access below)
Toll-like receptors (TLR) are important to pathogen recognition by a host and to the subsequent triggering of an innate immune response. Experimental and clinical evidence show that defects in TLR or in signaling pathways downstream from these receptors render hosts susceptible to various types of infection. TLR2 and TLR4 are involved in recognition of several fungi, such as Candida albicans, Aspergillus niger, Aspergillus fumigatus and Saccharomyces cerevisiae. However, no information is available about TLR recognition of Sporothrix schenckii. S. schenckii is a thermally dimorphic fungus, the causative agent of sporotrichosis, a mycotic infection characterized by frequent involvement of the skin and subcutaneous tissues; occasionally, it may also produce lesions of the internal organs mostly reported among immunocompromised hosts. Immune defense mechanisms, particularly cellmediated immunity have been reported to be important in infection resistance. The aim of this study was to assess the role of TLR4 in the response of macrophages to S. schenckii, using TLR4-deficient mice (C3H/HeJ) and control mice (C3H/HePas), evaluating immunological mediators produced by exudate peritoneal cells, TLR4 accessory protein expression, and apoptosis of these cells over a period of ten weeks. Reactive oxygen intermediates production was determined through phenol red oxidation method and has revealed that TLR4-defective mice produced lower levels of H2O2 than TLR4 normal mice. In these animals, higher H2O2 concentrations were seen when lipid extract obtained from S. schenckii mycelium was used. However, nitric oxide (NO) and cytokine production occurred in higher levels when cells were challenged with lipid extract from S. schenckii yeast cells, which is the morphotype found in the host during infection. NO and cytokines such as IL-1, TNF- and IL-10 production in culture supernatants were also lower... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Esporotricose, Apoptose - Teses, Citocina, Imunologia celular, Sporotrichosis, Immune response, Hydrogen peroxide, Nitric oxide, Cytokines, Apoptosis
Como citar
SASSÁ, Micheli Fernanda. Participação do receptor toll-like4 na resposta imune durante a esporotricose ecperimental. 2008. 182 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2008.