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Probiotic Lactobacillus rhamnosus GG mono-association suppresses human rotavirus-induced autophagy in the gnotobiotic piglet intestine.

Wu S, Yuan L, Zhang Y, Liu F, Li G, Wen K, Kocher J, Yang X, Sun J - Gut Pathog (2013)

Bottom Line: We found that LGG feeding did not increase autophagy, whereas virus infection induced autophagy in the piglet intestine.LGG treatment during viral gastroenteritis reduced autophagy marker expression to normal levels, induced apoptosis and partially prevented virus-induced tissue damage.A better understanding of the antiviral activity of LGG will lead to novel therapeutic strategies for infant infectious diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Rush University, Cohn Research Building, 1735 W, Harrison Street, Chicago, IL 60612, USA. jun_sun@rush.edu.

ABSTRACT

Background: Human rotavirus (HRV) is the most important cause of severe diarrhea in infants and young children. Probiotic Lactobacillus rhamnosus GG (LGG) reduces rotavirus infection and diarrhea. However, the molecular mechanisms of LGG-mediated protection from rotavirus infection are poorly understood. Autophagy plays an essential role in responses to microbial pathogens. However, the role of autophagy in HRV infection and LGG treatment is unknown. We hypothesize that rotavirus gastroenteritis activates autophagy and that LGG suppresses virus-induced autophagy and prevents intestinal damage in infected piglets.

Methods: We used LGG feeding to combat viral gastroenteritis in the gnotobiotic pig model of virulent HRV infection.

Results: We found that LGG feeding did not increase autophagy, whereas virus infection induced autophagy in the piglet intestine. Virus infection increased the protein levels of the autophagy markers ATG16L1 and Beclin-1 and the autophagy regulator mTOR. LGG treatment during viral gastroenteritis reduced autophagy marker expression to normal levels, induced apoptosis and partially prevented virus-induced tissue damage.

Conclusion: Our study provides new insights into virus-induced autophagy and LGG suppression of uncontrolled autophagy and intestinal injury. A better understanding of the antiviral activity of LGG will lead to novel therapeutic strategies for infant infectious diseases.

No MeSH data available.


Related in: MedlinePlus

LGG treatment protects intestine physiology after virus infection. (A) H&E staining of the pig ileum. Infiltration of immune cells (yellow arrow) and discontinued muscularis mucosae (green arrow) were present in pig ilea infected with HRV (10× magnification, scale bar 200 μm). (B) HRV increases claudin-2 protein in pig ileum. (C) Diagram showing the potential roles of LGG in HRV-infected pig ileum. While HRV increases autophagy to establish infection in epithelial cells, LGG inhibits autophagy and increases apoptosis to clear HRV-infected cells.
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Figure 5: LGG treatment protects intestine physiology after virus infection. (A) H&E staining of the pig ileum. Infiltration of immune cells (yellow arrow) and discontinued muscularis mucosae (green arrow) were present in pig ilea infected with HRV (10× magnification, scale bar 200 μm). (B) HRV increases claudin-2 protein in pig ileum. (C) Diagram showing the potential roles of LGG in HRV-infected pig ileum. While HRV increases autophagy to establish infection in epithelial cells, LGG inhibits autophagy and increases apoptosis to clear HRV-infected cells.

Mentions: LGG may suppress uncontrolled autophagy, thus protecting the intestine from injury during viral gastroenteritis. By H&E staining, we observed vigorous immune infiltration (yellow arrow) and discontinued muscularis mucosae (green arrow) in pig ileum infected with HRV (Figure 5A), but the LGG-treated infected ileum had less inflammation. LGG helped to maintain intestinal epithelial integrity. Claudin-2 is a ‘leaky’ claudin that forms a water channel, which mediates paracellular water transport in leaky epithelia [22-26]. Western blotting showed that virus infection increased the expression of claudin-2, whereas LGG treatment lowered the claudin-2 level after infection (Figure 5B). This result may explain our observations that LGG-treated piglets were less likely to develop HRV diarrhea and had a shorter mean duration of diarrhea compared with the non-treated group (data not shown). Our previous study and unpublished data showed that non-treated infected pigs had worse clinical and histopathological outcomes than the LGG+HRV group. Virus shedding was also lower in the LGG-treated pigs compared with the non-treated HRV group (data not shown).


Probiotic Lactobacillus rhamnosus GG mono-association suppresses human rotavirus-induced autophagy in the gnotobiotic piglet intestine.

Wu S, Yuan L, Zhang Y, Liu F, Li G, Wen K, Kocher J, Yang X, Sun J - Gut Pathog (2013)

LGG treatment protects intestine physiology after virus infection. (A) H&E staining of the pig ileum. Infiltration of immune cells (yellow arrow) and discontinued muscularis mucosae (green arrow) were present in pig ilea infected with HRV (10× magnification, scale bar 200 μm). (B) HRV increases claudin-2 protein in pig ileum. (C) Diagram showing the potential roles of LGG in HRV-infected pig ileum. While HRV increases autophagy to establish infection in epithelial cells, LGG inhibits autophagy and increases apoptosis to clear HRV-infected cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750464&req=5

Figure 5: LGG treatment protects intestine physiology after virus infection. (A) H&E staining of the pig ileum. Infiltration of immune cells (yellow arrow) and discontinued muscularis mucosae (green arrow) were present in pig ilea infected with HRV (10× magnification, scale bar 200 μm). (B) HRV increases claudin-2 protein in pig ileum. (C) Diagram showing the potential roles of LGG in HRV-infected pig ileum. While HRV increases autophagy to establish infection in epithelial cells, LGG inhibits autophagy and increases apoptosis to clear HRV-infected cells.
Mentions: LGG may suppress uncontrolled autophagy, thus protecting the intestine from injury during viral gastroenteritis. By H&E staining, we observed vigorous immune infiltration (yellow arrow) and discontinued muscularis mucosae (green arrow) in pig ileum infected with HRV (Figure 5A), but the LGG-treated infected ileum had less inflammation. LGG helped to maintain intestinal epithelial integrity. Claudin-2 is a ‘leaky’ claudin that forms a water channel, which mediates paracellular water transport in leaky epithelia [22-26]. Western blotting showed that virus infection increased the expression of claudin-2, whereas LGG treatment lowered the claudin-2 level after infection (Figure 5B). This result may explain our observations that LGG-treated piglets were less likely to develop HRV diarrhea and had a shorter mean duration of diarrhea compared with the non-treated group (data not shown). Our previous study and unpublished data showed that non-treated infected pigs had worse clinical and histopathological outcomes than the LGG+HRV group. Virus shedding was also lower in the LGG-treated pigs compared with the non-treated HRV group (data not shown).

Bottom Line: We found that LGG feeding did not increase autophagy, whereas virus infection induced autophagy in the piglet intestine.LGG treatment during viral gastroenteritis reduced autophagy marker expression to normal levels, induced apoptosis and partially prevented virus-induced tissue damage.A better understanding of the antiviral activity of LGG will lead to novel therapeutic strategies for infant infectious diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Rush University, Cohn Research Building, 1735 W, Harrison Street, Chicago, IL 60612, USA. jun_sun@rush.edu.

ABSTRACT

Background: Human rotavirus (HRV) is the most important cause of severe diarrhea in infants and young children. Probiotic Lactobacillus rhamnosus GG (LGG) reduces rotavirus infection and diarrhea. However, the molecular mechanisms of LGG-mediated protection from rotavirus infection are poorly understood. Autophagy plays an essential role in responses to microbial pathogens. However, the role of autophagy in HRV infection and LGG treatment is unknown. We hypothesize that rotavirus gastroenteritis activates autophagy and that LGG suppresses virus-induced autophagy and prevents intestinal damage in infected piglets.

Methods: We used LGG feeding to combat viral gastroenteritis in the gnotobiotic pig model of virulent HRV infection.

Results: We found that LGG feeding did not increase autophagy, whereas virus infection induced autophagy in the piglet intestine. Virus infection increased the protein levels of the autophagy markers ATG16L1 and Beclin-1 and the autophagy regulator mTOR. LGG treatment during viral gastroenteritis reduced autophagy marker expression to normal levels, induced apoptosis and partially prevented virus-induced tissue damage.

Conclusion: Our study provides new insights into virus-induced autophagy and LGG suppression of uncontrolled autophagy and intestinal injury. A better understanding of the antiviral activity of LGG will lead to novel therapeutic strategies for infant infectious diseases.

No MeSH data available.


Related in: MedlinePlus