Breuilh Laetitia, Vanhoutte François, Fontaine Josette, van Stijn Caroline M W, Tillie-Leblond Isabelle, Capron Monique, Faveeuw Christelle, Jouault Thierry, van Die Irma, Gosset Philippe, Trottein François
Institut National de la Recherche Médicale, U547, France.
Infect Immun. 2007 Nov;75(11):5148-57. doi: 10.1128/IAI.02006-06. Epub 2007 Sep 4.
Galectin-3 (Gal-3) is a multifunctional beta-galactoside-binding lectin that senses self-derived and microbial glycoconjugates. Although Gal-3 is important in immune reactions and host defense in some experimental models, the function of Gal-3 during helminthic diseases (e.g., schistosomiasis) is still elusive. We show that, compared to wild-type Schistosoma mansoni-infected mice, infected Gal-3-/- mice have a reduced number of T and B lymphocytes in the spleen, develop reduced liver granulomas at 7 weeks (acute phase) and 14 weeks (chronic phase) postinfection, and mount a biased cellular and humoral Th1 response. In an attempt to understand this latter phenomenon, we studied the role of endogenous Gal-3 in dendritic cells (DCs), the most potent antigen-presenting cells, both in vitro and in vivo. Although Gal-3 deficiency in DCs does not impact their differentiation and maturation processes, it greatly influences the strength (but not the nature) of the adaptive immune response that they trigger, suggesting that Gal-3 deficiency in some other cell types may be important during murine schistosomiasis. As a whole, this study implies that Gal-3 is a modulator of the immune/inflammatory responses during helminthic infection and reveals for the first time that Gal-3 expression in DCs is pivotal to control the magnitude of T-lymphocyte priming.
半乳糖凝集素-3(Gal-3)是一种多功能的β-半乳糖苷结合凝集素,可识别自身来源和微生物的糖缀合物。尽管在某些实验模型中Gal-3在免疫反应和宿主防御中很重要,但Gal-3在蠕虫病(如血吸虫病)中的功能仍不清楚。我们发现,与感染曼氏血吸虫的野生型小鼠相比,感染的Gal-3基因敲除小鼠脾脏中的T淋巴细胞和B淋巴细胞数量减少,在感染后7周(急性期)和14周(慢性期)肝脏肉芽肿形成减少,并且产生偏向性的细胞和体液Th1反应。为了理解后一种现象,我们在体外和体内研究了内源性Gal-3在树突状细胞(DCs)中的作用,树突状细胞是最有效的抗原呈递细胞。尽管DCs中Gal-3的缺乏并不影响其分化和成熟过程,但它极大地影响了它们触发的适应性免疫反应的强度(而非性质),这表明在小鼠血吸虫病期间,其他一些细胞类型中Gal-3的缺乏可能很重要。总体而言,这项研究表明Gal-3是蠕虫感染期间免疫/炎症反应的调节剂,并首次揭示DCs中Gal-3的表达对于控制T淋巴细胞启动的强度至关重要。