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细胞因子和过氧化氢对系统性实验性感染中申克孢子丝菌外抗原的反应

Response of Cytokines and Hydrogen Peroxide to Sporothrix schenckii Exoantigen in Systemic Experimental Infection.

作者信息

Maia Danielle Cardoso Geraldo, Gonçalves Amanda Costa, Ferreira Lucas Souza, Manente Francine Alessandra, Portuondo Deivys Leandro, Vellosa José Carlos Rebuglio, Polesi Marisa Campos, Batista-Duharte Alexander, Carlos Iracilda Zeppone

机构信息

Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista "Júlio de Mesquita Filho" - UNESP, Rua Expedicionários do Brasil n° 1621, Araraquara, SP, CEP 14.801-902, Brazil.

Departamento de Análises Clínicas e Toxicológicas, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa - UEPG, Ponta Grossa, PR, Brazil.

出版信息

Mycopathologia. 2016 Apr;181(3-4):207-15. doi: 10.1007/s11046-015-9966-2. Epub 2015 Nov 24.

Abstract

The response of hydrogen peroxide (H2O2) and cytokines during an experimental sporotrichosis in male Swiss mice was assessed over a period of 10 weeks by monitoring macrophage activation challenged with exoantigen (ExoAg) from the fungus Sporothrix schenckii. The studied endpoints were: H2O2 production, fungal burden at spleen, apoptosis in peritoneal macrophages, and IL-1β, IL-6, IL-2, IL-10 production. During the two first weeks of infection was observed low burden of yeast in spleen and high response of H2O2, IL-2, and IL-1β. The weeks of highest fungal burden (fourth-sixth) coincided with major apoptosis in peritoneal macrophages, normal production of IL-6 and lower production of H2O2, IL-2, and IL-1β, suggesting a role for these three last in the early control of infection. On the other hand, IL-1β (but not IL-6) was recovered since the sixth week, suggesting a possible role in the late phase of infection, contributing to the fungal clearance in conjunction with the specific mechanisms. The IL-10 was elevated until the sixth, principally in the second week. These results evidences that ExoAg is involved in the host immune modulation, influencing the S. Schenckii virulence, and its role is related with the time of the infection in the model used.

摘要

通过监测用申克孢子丝菌外抗原(ExoAg)刺激的巨噬细胞活化情况,在10周的时间里评估了雄性瑞士小鼠实验性孢子丝菌病期间过氧化氢(H2O2)和细胞因子的反应。研究的终点指标包括:H2O2产生量、脾脏中的真菌负荷、腹膜巨噬细胞凋亡以及IL-1β、IL-6、IL-2、IL-10的产生量。在感染的前两周,脾脏中酵母负荷较低,H2O2、IL-2和IL-1β反应较高。真菌负荷最高的几周(第四至六周)与腹膜巨噬细胞的主要凋亡、IL-6的正常产生以及H2O2、IL-2和IL-1β的较低产生相吻合,这表明后三者在感染的早期控制中起作用。另一方面,自第六周起IL-1β(而非IL-6)恢复,提示其可能在感染后期起作用,与特定机制共同促进真菌清除。IL-10在第六周前升高,主要在第二周。这些结果证明ExoAg参与宿主免疫调节,影响申克孢子丝菌的毒力,其作用与所用模型中的感染时间有关。

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