Homeostasis and function of goblet cells during roltavirus infection in mice
Homeostasis and function of goblet cells during roltavirus infection in mice
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DOI：
10.1016/j.virol.2005.03.039
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发表时间：
2005-07-05
期刊：
影响因子：
3.7
通讯作者：
Einerhand, AWC
中科院分区：
文献类型：
--
作者：
Boshuizen, JA;Reimerink, JHJ;Einerhand, AWC
轮状病毒是导致幼儿严重病毒性胃肠炎的主要原因。为了深入了解轮状病毒感染期间杯状细胞稳态和肠粘蛋白表达，用鼠轮状病毒接种6日龄小鼠。为了确定上皮细胞迁移，在接种前给小鼠注射BrdU。小肠在感染后不同的日子（dpi）分离和评价轮状病毒和杯状细胞特异性基因表达。分离对照和感染动物在感染后1、2和4天的小肠粘蛋白，并测试其体外中和轮状病毒感染的能力。接种后，在1和4 dpi观察到两个病毒复制高峰。在感染过程中，感染小鼠十二指肠和空肠的杯状细胞数量减少，但在回肠不受影响。感染动物的杯状细胞聚集在绒毛的顶端。Muc 2 mRNA水平在1 dpi病毒复制高峰期间增加，而在其他时间点Muc 2和Tff 3 mRNA水平维持在对照水平。组织中的Muc 2蛋白水平也得以维持，然而Tff 3蛋白水平显著降低。含硫酸粘蛋白的杯状细胞在两个感染高峰期减少。从对照和感染小鼠中分离的粘蛋白在体外有效地中和轮状病毒感染。此外，从感染后4天的小鼠中分离的粘蛋白在抑制轮状病毒感染方面比从感染后4天的对照小鼠中分离的粘蛋白更有效。总之，这些数据表明，在轮状病毒感染，杯状细胞，肠上皮细胞相比，相对免于凋亡，特别是在回肠。杯状细胞特异性Muc 2表达增加，并且在感染过程中粘蛋白结构被修饰。这表明，杯状细胞和粘蛋白在主动防御轮状病毒感染中发挥作用，并且粘蛋白数量、组成和/或结构的年龄依赖性差异改变了小肠粘蛋白的抗病毒能力。(c)2005年爱思唯尔公司All rights reserved.
Rotaviruses are the leading cause of severe viral gastroenteritis in young children. To gain insight in goblet cell homeostasis and intestinal mucin expression during rotavirus infection, 6-day-old mice were inoculated with murine rotavirus. To determine epithelial cell migration, mice were injected with BrdU just before inoculation. Small intestines were isolated at different days postinfection (dpi) and evaluated for rotavirus and goblet cell-specific gene expression. Small intestinal mucins of control and infected animals at 1, 2, and 4 dpi were isolated and tested for their capability to neutralize rotavirus infection in vitro. After inoculation, two peaks of viral replication were observed at 1 and 4 dpi. During infection, the number of goblet cells in infected mice was decreased in duodenum and jejunum, but was unaffected in the ileum. Goblet cells in infected animals accumulated at the tips of the villi. Muc2 mRNA levels were increased during the peak of viral replication at 1 dpi, whereas at other time points Muc2 and Tff3 mRNA levels were maintained at control levels. Muc2 protein levels in the tissue were also maintained, however Tff3 protein levels were strongly decreased. The number of goblet cells containing sulfated mucins Was reduced during the two peaks of infection. Mucins isolated at 1 and 2 dpi from control and infected mice efficiently neutralized rotavirus infection in vitro. Moreover, mucins isolated from infected mice at 4 dpi were more potent in inhibiting rotavirus infection than mucins from control mice at 4 dpi. In conclusion, these data show that during rotavirus infection, goblet cells, in contrast to enterocytes, are relatively spared from apoptosis especially in the ileum. Goblet cell-specific Muc2 expression is increased and mucin structure is modified in the course of infection. This suggests that goblet cells and mucins play a role in the active defense against rotavirus infection and that age-dependent differences in mucin quantities, composition, and/or structure alter the anti-viral capabilities of small intestinal mucins. (c) 2005 Elsevier Inc. All rights reserved.