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Mucin dynamics in intestinal bacterial infection.

Lindén SK, Florin TH, McGuckin MA - PLoS ONE (2008)

Bottom Line: 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.Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

View Article: PubMed Central - PubMed

Affiliation: Mucosal Diseases Program, Mater Medical Research Institute, Mater Health Services, South Brisbane, Queensland, Australia.

ABSTRACT

Background: 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.

Conclusion: Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

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Related in: MedlinePlus

Tissue localization of mucins in small intestine and caecum.Histologically, the small intestinal villi and caecal crypts are covered by a simple columnar epithelium consisting of enterocytes with interspersed goblet cells. Using immunohistochemistry, we demonstrated that the apical surface of small intestine and caecal epithelia are lined by the cell surface mucins Muc13 and Muc17 as well as a small amount of Muc4 (brown). The goblet cells contain alcian blue positive material (blue), which mainly is Muc2 (brown), but also some Muc4. The photographs were taken using a 20× magnification. The quantification scores for any of these mucins were not significantly different between non-infected mice (○) and mice infected with C. rodentium for 12 days (•) in these areas of the intestine. (Mann Whitney U test, n = 7). SCL = subcellular localization, RC = region of crypt. The mucin stains are shown in serial sections on the same tissue area, whereas the mucin stain scores represent the average stain scores for the entire specimen for each individual mouse.
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pone-0003952-g003: Tissue localization of mucins in small intestine and caecum.Histologically, the small intestinal villi and caecal crypts are covered by a simple columnar epithelium consisting of enterocytes with interspersed goblet cells. Using immunohistochemistry, we demonstrated that the apical surface of small intestine and caecal epithelia are lined by the cell surface mucins Muc13 and Muc17 as well as a small amount of Muc4 (brown). The goblet cells contain alcian blue positive material (blue), which mainly is Muc2 (brown), but also some Muc4. The photographs were taken using a 20× magnification. The quantification scores for any of these mucins were not significantly different between non-infected mice (○) and mice infected with C. rodentium for 12 days (•) in these areas of the intestine. (Mann Whitney U test, n = 7). SCL = subcellular localization, RC = region of crypt. The mucin stains are shown in serial sections on the same tissue area, whereas the mucin stain scores represent the average stain scores for the entire specimen for each individual mouse.

Mentions: AB stains acidic mucins blue and the PAS stains neutral mucins pink whilst mixtures of neutral and acidic mucins appear purple. In the small intestine, the goblet cells varied from purple to blue and tended to be bluer towards the bottom of the crypts with more purple/fushia towards the top (Figure 3), indicating that the carbohydrates are more highly charged towards the bottom of the crypts. All goblet cells expressed Muc2 and most of the villous goblet cells expressed Muc4 with weaker staining in the crypt goblet cells. Enterocytes expressed the Muc4, Muc13 and Muc17 mucins, but not Muc1, with the Muc13 antibody giving the strongest stain, which decorated the surface of the entire glandular and villous epithelium. The presence of Muc4 in goblet cells and enterocytes is similar to that described for human tissue, and is consistent with previously published work showing that MUC4 can be produced both in membrane bound and soluble forms [40], [41]. No discernable changes were seen in expression of any of the mucins in the infected small intestine, despite the presence of a low density of C. rodentium.


Mucin dynamics in intestinal bacterial infection.

Lindén SK, Florin TH, McGuckin MA - PLoS ONE (2008)

Tissue localization of mucins in small intestine and caecum.Histologically, the small intestinal villi and caecal crypts are covered by a simple columnar epithelium consisting of enterocytes with interspersed goblet cells. Using immunohistochemistry, we demonstrated that the apical surface of small intestine and caecal epithelia are lined by the cell surface mucins Muc13 and Muc17 as well as a small amount of Muc4 (brown). The goblet cells contain alcian blue positive material (blue), which mainly is Muc2 (brown), but also some Muc4. The photographs were taken using a 20× magnification. The quantification scores for any of these mucins were not significantly different between non-infected mice (○) and mice infected with C. rodentium for 12 days (•) in these areas of the intestine. (Mann Whitney U test, n = 7). SCL = subcellular localization, RC = region of crypt. The mucin stains are shown in serial sections on the same tissue area, whereas the mucin stain scores represent the average stain scores for the entire specimen for each individual mouse.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2601037&req=5

pone-0003952-g003: Tissue localization of mucins in small intestine and caecum.Histologically, the small intestinal villi and caecal crypts are covered by a simple columnar epithelium consisting of enterocytes with interspersed goblet cells. Using immunohistochemistry, we demonstrated that the apical surface of small intestine and caecal epithelia are lined by the cell surface mucins Muc13 and Muc17 as well as a small amount of Muc4 (brown). The goblet cells contain alcian blue positive material (blue), which mainly is Muc2 (brown), but also some Muc4. The photographs were taken using a 20× magnification. The quantification scores for any of these mucins were not significantly different between non-infected mice (○) and mice infected with C. rodentium for 12 days (•) in these areas of the intestine. (Mann Whitney U test, n = 7). SCL = subcellular localization, RC = region of crypt. The mucin stains are shown in serial sections on the same tissue area, whereas the mucin stain scores represent the average stain scores for the entire specimen for each individual mouse.
Mentions: AB stains acidic mucins blue and the PAS stains neutral mucins pink whilst mixtures of neutral and acidic mucins appear purple. In the small intestine, the goblet cells varied from purple to blue and tended to be bluer towards the bottom of the crypts with more purple/fushia towards the top (Figure 3), indicating that the carbohydrates are more highly charged towards the bottom of the crypts. All goblet cells expressed Muc2 and most of the villous goblet cells expressed Muc4 with weaker staining in the crypt goblet cells. Enterocytes expressed the Muc4, Muc13 and Muc17 mucins, but not Muc1, with the Muc13 antibody giving the strongest stain, which decorated the surface of the entire glandular and villous epithelium. The presence of Muc4 in goblet cells and enterocytes is similar to that described for human tissue, and is consistent with previously published work showing that MUC4 can be produced both in membrane bound and soluble forms [40], [41]. No discernable changes were seen in expression of any of the mucins in the infected small intestine, despite the presence of a low density of C. rodentium.

Bottom Line: 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.Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

View Article: PubMed Central - PubMed

Affiliation: Mucosal Diseases Program, Mater Medical Research Institute, Mater Health Services, South Brisbane, Queensland, Australia.

ABSTRACT

Background: 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.

Conclusion: Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

Show MeSH
Related in: MedlinePlus