Toxoplasma gondii infection reveals a novel regulatory role for galectin-3 in the interface of innate and adaptive immunity

Toxoplasma gondii infection reveals a novel regulatory role for galectin-3 in the interface of innate and adaptive immunity
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DOI:
10.2353/ajpath.2006.050636
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发表时间:
2006-06-01
影响因子:
6
通讯作者:
Roque-Barreira, Maria Cristina
Roque-Barreira, Maria Cristina
中科院分区:
医学2区
文献类型:
--
作者:
Bernardes, Emerson Soares;Silva, Neide M.;Roque-Barreira, Maria Cristina

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为了探讨半乳糖凝集素-3在先天免疫中的作用,我们研究了半乳糖凝集素-3缺陷(gal 3(-/-))小鼠对弓形虫感染的反应,其特征在于受影响器官的炎症,Th-1极化免疫反应和中枢神经系统囊肿的积累。在口服感染的野生型(Gal 3(+/+))小鼠中,半乳糖凝集素-3在浸润肠、肝、肺和脑的白细胞中高度表达。与gal 3(+/+)相比,感染gal 3(-/-)的小鼠在除肺以外的所有这些器官中产生了减少的炎症反应。gal 3(-/-)小鼠的脑显示浸润的单核细胞/巨噬细胞和CD 8(+)细胞的数量显著减少,寄生虫负荷更高。此外,gal 3-/-小鼠安装一个更高的Th 1极化反应,并有相当的生存率经口弓形虫感染,即使他们更容易腹腔感染。有趣的是,来自gal 3(-/-)小鼠的脾细胞和纯化的CD 11 c(+)树突状细胞比来自gal 3(+/+)小鼠的细胞产生更高量的白细胞介素-12,这可能解释了在gal 3-/-小鼠中验证的更高的Th 1应答。我们的结论是,半乳糖凝集素-3发挥了重要的作用,在先天免疫,不仅包括促炎作用,但也对树突状细胞的调节作用,能够干扰适应性免疫反应。
In attempts to investigate the role of galectin-3 in innate immunity, we studied galectin-3-deficient (gal3(-/-)) mice with regard to their response to Toxoplasma gondii infection, which is characterized by inflammation in affected organs, Th-1-polarized immune response, and accumulation of cysts in the central nervous system. in wild-type (gal3(+/+)) mice, infected orally, galectin-3 was highly expressed in the leukocytes infiltrating the intestines, liver, lungs, and brain. Compared with gal3(+/+), infected gal3(-/-) mice developed reduced inflammatory response in all of these organs but the lungs. Brain of gal3(-/-) mice displayed a significantly reduced number of infiltrating monocytes/macrophages and CD8(+) cells and a higher parasite burden. Furthermore, gal3-/- mice mounted a higher Th1-polarized response and had comparable survival rates on peroral T gondii infection, even though they were more susceptible to intraperitoneal infection. Interestingly, splenic cells and purified CD11c(+) dendritic cells from gal3(-/-) mice produced higher amounts of interleukin-12 than cells from gal3(+/+) mice, possibly explaining the higher Th1 response verified in the gal3-/- mice. We conclude that galectin-3 exerts an important role in innate immunity, including not only a proinflammatory effect but also a regulatory role on dendritic cells, capable of interfering in the adaptive immune response.