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抗申克孢子丝菌抗体可增强巨噬细胞产生肿瘤坏死因子-α及杀伤能力。

Antibodies Against Sporothrix schenckii Enhance TNF-α Production and Killing by Macrophages.

作者信息

Franco D de Lima, Nascimento R C, Ferreira K S, Almeida S R

机构信息

Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, BrazilLaboratório de Micologia Celular e Proteômica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Ciências Biológicas, UNIFESP, São Paulo, Brazil.

出版信息

Scand J Immunol. 2012 Feb;75(2):142-6. doi: 10.1111/j.1365-3083.2011.02636.x.

Abstract

Sporotrichosis is a chronic granulomatous mycosis caused by the dimorphic fungus Sporothrix schenckii. The immunological mechanisms involved in the prevention and control of sporotrichosis suggest that cell-mediated immunity plays an important role in protecting the host against S. schenckii. Nonetheless, recent data strongly support the existence of protective Abs against this pathogenic fungus. In a previous study, we showed that passive Ab therapy led to a significant reduction in the number of colony forming unit in the organs of mice when the MAb was injected before and during S. schenckii infection. The ability of opsonization to enhance macrophage damage to S. schenckii and subsequent cytokine production was investigated in this work. Here we show that the fungicidal characteristics of macrophages are increased when the fungus is phagocytosed in the presence of inactivated serum from mice infected with S. schenckii or mAb anti-gp70. Additionally, we show an increase in the levels of pro-inflammatory cytokines such as TNF-α and IL-1β. This study provides additional support for the importance of antibodies in protecting against S. schenckii and concludes that opsonization is an important process to increase TNF-α production and fungus killing by macrophages in experimental sporotrichosis.

摘要

孢子丝菌病是由双相真菌申克孢子丝菌引起的一种慢性肉芽肿性真菌病。参与孢子丝菌病预防和控制的免疫机制表明,细胞介导的免疫在保护宿主抵御申克孢子丝菌方面发挥着重要作用。尽管如此,最近的数据有力地支持了针对这种致病真菌存在保护性抗体。在先前的一项研究中,我们表明,当在申克孢子丝菌感染之前和期间注射单克隆抗体时,被动抗体疗法可显著减少小鼠器官中的菌落形成单位数量。在这项工作中,研究了调理作用增强巨噬细胞对申克孢子丝菌的损伤及随后细胞因子产生的能力。在此我们表明,当真菌在存在来自感染申克孢子丝菌的小鼠的灭活血清或抗gp70单克隆抗体的情况下被吞噬时,巨噬细胞的杀菌特性会增强。此外,我们还发现促炎细胞因子如TNF-α和IL-1β的水平有所增加。本研究为抗体在抵御申克孢子丝菌中的重要性提供了额外支持,并得出结论:调理作用是增加实验性孢子丝菌病中TNF-α产生和巨噬细胞杀灭真菌的重要过程。

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