Lindén Sara K, Florin Timothy H J, McGuckin Michael A
Mucosal Diseases Program, Mater Medical Research Institute, Mater Health Services, South Brisbane, Queensland, Australia.
PLoS One. 2008;3(12):e3952. doi: 10.1371/journal.pone.0003952. Epub 2008 Dec 17.
Bacterial gastroenteritis causes morbidity and mortality in humans worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis caused by the human pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract.
METHODOLOGY/PRINCIPAL FINDINGS: Using Immunohistochemistry, we investigated intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13 and Muc3/17) in healthy and C. rodentium infected mice. The majority of the C. rodentium infected mice developed systemic infection and colitis in the mid and distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface. In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals. In the distal colonic epithelium, all secreted and cell surface mucins decreased with the exception of the Muc1 cell surface mucin which increased after infection (p<0.05). Similarly, during human infection Salmonella St Paul, Campylobacter jejuni and Clostridium difficile induced MUC1 in the colon.
Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.
细菌性肠胃炎在全球范围内导致人类发病和死亡。鼠柠檬酸杆菌感染是由人类病原体肠致病性大肠杆菌和肠出血性大肠杆菌引起的肠胃炎的模型。粘蛋白糖蛋白是细菌在肠道中遇到的第一道屏障的主要成分。
方法/主要发现:我们使用免疫组织化学方法,研究了健康小鼠和感染鼠柠檬酸杆菌的小鼠肠道中粘蛋白(阿尔辛蓝/过碘酸希夫染色、Muc1、Muc2、Muc4、Muc5AC、Muc13和Muc3/17)的表达情况。到第12天时,大多数感染鼠柠檬酸杆菌的小鼠出现全身感染和结肠中、远端的结肠炎。鼠柠檬酸杆菌在体外与主要分泌型粘蛋白Muc2结合,并且在感染动物体内的分泌型MUC2中发现大量细菌,这表明粘蛋白可能会限制细菌接触上皮表面。在小肠、盲肠和近端结肠中,感染和未感染动物的粘蛋白表达相似。在远端结肠上皮中,除了感染后增加的Muc1细胞表面粘蛋白外,所有分泌型和细胞表面粘蛋白均减少(p<0.05)。同样,在人类感染圣保罗沙门氏菌、空肠弯曲菌和艰难梭菌期间,结肠中会诱导MUC1表达。
肠道感染会导致细胞表面和分泌型粘蛋白发生重大变化。