Departamento de Ciencias Biologicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.
Millennium Nucleus in the Biology of Intestinal Microbiota, Santiago, Chile.
Front Immunol. 2019 Apr 2;10:610. doi: 10.3389/fimmu.2019.00610. eCollection 2019.
Currently, inflammatory bowel disease (IBD) is a serious public health problem on the rise worldwide. In this work, we utilized the zebrafish to introduce a new model of intestinal inflammation triggered by food intake. Taking advantage of the translucency of the larvae and the availability of transgenic zebrafish lines with fluorescently labeled macrophages, neutrophils, or lymphocytes, we studied the behavior of these cell types during the course of inflammation. We established two feeding strategies, the first using fish that were not previously exposed to food (naïve strategy) and the second in which fish were initially exposed to normal food (developed strategy). In both strategies, we analyzed the effect of subsequent intake of a control or a soybean meal diet. Our results showed increased numbers of innate immune cells in the gut in both the naïve or developed protocols. Likewise, macrophages underwent drastic morphological changes after feeding, switching from a small and rounded contour to a larger and dendritic shape. Lymphocytes colonized the intestine as early as 5 days post fertilization and increased in numbers during the inflammatory process. Gene expression analysis indicated that lymphocytes present in the intestine correspond to T helper cells. Interestingly, control diet only induced a regulatory T cell profile in the developed model. On the contrary, soybean meal diet induced a Th17 response both in naïve and developed model. In addition, when feeding was performed in -deficient fish, intestinal inflammation was not induced indicating that inflammation induced by soybean meal is T cell-dependent.
目前,炎症性肠病(IBD)是全球范围内日益严重的公共卫生问题。在这项工作中,我们利用斑马鱼引入了一种新的由食物摄入引发的肠道炎症模型。利用幼虫的透明性以及具有荧光标记巨噬细胞、中性粒细胞或淋巴细胞的转基因斑马鱼系的可用性,我们研究了这些细胞类型在炎症过程中的行为。我们建立了两种喂养策略,第一种使用以前未接触过食物的鱼(幼稚策略),第二种在鱼最初接触正常食物(开发策略)。在这两种策略中,我们分析了随后摄入对照或豆粕饮食的效果。我们的结果表明,在幼稚或开发方案中,肠道中的固有免疫细胞数量增加。同样,巨噬细胞在进食后经历了剧烈的形态变化,从小而圆的轮廓转变为更大的树突状形状。淋巴细胞早在受精后 5 天就定植在肠道中,并在炎症过程中数量增加。基因表达分析表明,肠道中的淋巴细胞对应于辅助性 T 细胞。有趣的是,对照饮食仅在开发模型中诱导调节性 T 细胞表型。相反,豆粕饮食在幼稚和开发模型中均诱导 Th17 反应。此外,当在 -缺陷鱼中进行喂养时,不会诱导肠道炎症,表明豆粕诱导的炎症依赖于 T 细胞。