Alonso-Trujillo Javier, Rivera-Montoya Irma, Rodríguez-Sosa Miriam, Terrazas Luis I
Laboratory of Immunoparasitology, Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios # 1, Los Reyes Iztacala, 54090 Tlalnepantla, Edo. de México, Mexico.
Parasitol Res. 2007 May;100(6):1341-50. doi: 10.1007/s00436-006-0424-4. Epub 2007 Jan 6.
The immune mechanisms that underlie resistance and susceptibility to cysticercosis are not completely understood. In this paper, using susceptible BALB/c mice and resistant STAT6-/-BALB/c mice, we have analyzed the role of nitric oxide (NO) in determining the outcome of murine cysticercosis caused by the cestode Taenia crassiceps. After T. crassiceps infection, wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, IL-5, IL-4, and discrete levels of NO, and remained susceptible to T. crassiceps infection. In contrast, similarly infected BALB/c mice treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) mounted a similar immune response but with lower levels of NO and harbored nearly 100% more parasites than N(omega)-nitro-D-arginine methyl ester (D-NAME, inactive enantiomer)-treated mice. To further analyze the role of NO in murine cysticercosis, we treated STAT6-/-male mice (known to be highly resistant to T. crassiceps) with L-NAME during 8 weeks of infection. As expected, STAT6-/-mice mounted a strong Th1-like response, produced high levels of IgG2a, IFN-gamma, and IL-17, whereas their macrophages displayed increased transcripts of tumor necrosis factor (TNF)-alpha as well as inducible nitric oxide synthase (iNOS) and efficiently controlled T. crassiceps infection. However, STAT6-/-male mice receiving L-NAME mounted a similar immune response but with lower iNOS transcripts concomitantly with decreased levels of NO in sera and displayed significantly higher parasite burdens. These findings suggest that macrophage activation and NO production are effector mechanisms that importantly contribute in host resistance to T. crassiceps infection. The immune mechanisms that underlie resistance and susceptibility to cysticercosis are not completely understood. In this paper, using susceptible BALB/c mice and resistant STAT6-/-BALB/c mice, we have analyzed the role of nitric oxide (NO) in determining the outcome of murine cysticercosis caused by the cestode Taenia crassiceps. After T. crassiceps infection, wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, IL-5, IL-4, and discrete levels of NO, and remained susceptible to T. crassiceps infection. In contrast, similarly infected BALB/c mice treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) mounted a similar immune response but with lower levels of NO and harbored nearly 100% more parasites than N(omega)-nitro-d-arginine methyl ester (D-NAME, inactive enantiomer)-treated mice. To further analyze the role of NO in murine cysticercosis, we treated STAT6-/-male mice (known to be highly resistant to T. crassiceps) with L-NAME during 8 weeks of infection. As expected, STAT6-/-mice mounted a strong Th1-like response, produced high levels of IgG2a, IFN-gamma, and IL-17, whereas their macrophages displayed increased transcripts of tumor necrosis factor (TNF)-alpha as well as inducible nitric oxide synthase (iNOS) and efficiently controlled T. crassiceps infection. However, STAT6-/-male mice receiving L-NAME mounted a similar immune response but with lower iNOS transcripts concomitantly with decreased levels of NO in sera and displayed significantly higher parasite burdens. These findings suggest that macrophage activation and NO production are effector mechanisms that importantly contribute in host resistance to T. crassiceps infection.
目前尚不完全清楚对囊尾蚴病产生抗性和易感性的免疫机制。在本文中,我们使用易感性BALB/c小鼠和抗性STAT6-/-BALB/c小鼠,分析了一氧化氮(NO)在决定由绦虫粗颈绦虫引起的小鼠囊尾蚴病结局中的作用。粗颈绦虫感染后,野生型BALB/c小鼠产生强烈的Th2样反应,产生高水平的IgG1、IgE、IL-5、IL-4以及离散水平的NO,并对粗颈绦虫感染保持易感性。相比之下,用N(ω)-硝基-L-精氨酸甲酯(L-NAME,一种NO合酶抑制剂)处理的同样感染的BALB/c小鼠产生了类似的免疫反应,但NO水平较低,并且比用N(ω)-硝基-D-精氨酸甲酯(D-NAME,无活性对映体)处理的小鼠多携带近100%的寄生虫。为了进一步分析NO在小鼠囊尾蚴病中的作用,我们在感染的8周期间用L-NAME处理STAT6-/-雄性小鼠(已知对粗颈绦虫具有高度抗性)。正如预期的那样,STAT6-/-小鼠产生了强烈的Th1样反应,产生高水平的IgG2a、IFN-γ和IL-17,而它们的巨噬细胞显示肿瘤坏死因子(TNF)-α以及诱导型一氧化氮合酶(iNOS)的转录本增加,并有效控制了粗颈绦虫感染。然而,接受L-NAME的STAT6-/-雄性小鼠产生了类似的免疫反应,但iNOS转录本较低,同时血清中NO水平降低,并且显示出明显更高的寄生虫负荷。这些发现表明,巨噬细胞活化和NO产生是在宿主抵抗粗颈绦虫感染中起重要作用的效应机制。目前尚不完全清楚对囊尾蚴病产生抗性和易感性的免疫机制。在本文中,我们使用易感性BALB/c小鼠和抗性STAT6-/-BALB/c小鼠,分析了一氧化氮(NO)在决定由绦虫粗颈绦虫引起的小鼠囊尾蚴病结局中的作用。粗颈绦虫感染后,野生型BALB/c小鼠产生强烈的Th2样反应,产生高水平的IgG1、IgE、IL-5、IL-4以及离散水平的NO,并对粗颈绦虫感染保持易感性。相比之下,用N(ω)-硝基-L-精氨酸甲酯(L-NAME,一种NO合酶抑制剂)处理的同样感染的BALB/c小鼠产生了类似的免疫反应,但NO水平较低,并且比用N(ω)-硝基-D-精氨酸甲酯(D-NAME,无活性对映体)处理的小鼠多携带近100%的寄生虫。为了进一步分析NO在小鼠囊尾蚴病中的作用,我们在感染的8周期间用L-NAME处理STAT6-/-雄性小鼠(已知对粗颈绦虫具有高度抗性)。正如预期的那样,STAT6-/-小鼠产生了强烈的Th1样反应,产生高水平的IgG2a、IFN-γ和IL-17,而它们的巨噬细胞显示肿瘤坏死因子(TNF)-α以及诱导型一氧化氮合酶(iNOS)的转录本增加,并有效控制了粗颈绦虫感染。然而,接受L-NAME的STAT6-/-雄性小鼠产生了类似的免疫反应,但iNOS转录本较低,同时血清中NO水平降低,并且显示出明显更高的寄生虫负荷。这些发现表明,巨噬细胞活化和NO产生是在宿主抵抗粗颈绦虫感染中起重要作用的效应机制。