Limits...
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

Detection of p-mTOR, VPS34 and lysozyme proteins by immunofluorescence in pig ileum. (A) HRV increases the expression of p-mTOR (Ser 2448) in pig ileum. Red, p-mTOR. (B) HRV increases the expression of VPS34 in Gn pig ileum. Red, VPS34. (C) HRV with/without LGG increases the expression of lysozyme in Gn pig ileum. Red, lysozyme; blue, DAPI (20× magnification, scale bar 100 μm).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3750464&req=5

Figure 3: Detection of p-mTOR, VPS34 and lysozyme proteins by immunofluorescence in pig ileum. (A) HRV increases the expression of p-mTOR (Ser 2448) in pig ileum. Red, p-mTOR. (B) HRV increases the expression of VPS34 in Gn pig ileum. Red, VPS34. (C) HRV with/without LGG increases the expression of lysozyme in Gn pig ileum. Red, lysozyme; blue, DAPI (20× magnification, scale bar 100 μm).

Mentions: We next investigated the location of autophagy markers in the pig ileum. In the mock control and LGG only groups, we noticed few p-mTOR-positive cells (Figure 3A). In the HRV-infected intestine, p-mTOR staining was more prevalent. LGG treatment decreased the number of p-mTOR-positive cells in HRV-infected intestine. VPS34 levels were similar to those of p-mTOR; LGG treatment suppressed the number of VPS34-positive cells (Figure 3B). Furthermore, immunostaining showed that lysozyme was increased in ilea from HRV and LGG+HRV pigs compared with mock and LGG only pigs (Figure 3C), which was consistent with the real-time PCR result that rotavirus infection induced high levels of lysozyme mRNA (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)

Detection of p-mTOR, VPS34 and lysozyme proteins by immunofluorescence in pig ileum. (A) HRV increases the expression of p-mTOR (Ser 2448) in pig ileum. Red, p-mTOR. (B) HRV increases the expression of VPS34 in Gn pig ileum. Red, VPS34. (C) HRV with/without LGG increases the expression of lysozyme in Gn pig ileum. Red, lysozyme; blue, DAPI (20× magnification, scale bar 100 μm).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Detection of p-mTOR, VPS34 and lysozyme proteins by immunofluorescence in pig ileum. (A) HRV increases the expression of p-mTOR (Ser 2448) in pig ileum. Red, p-mTOR. (B) HRV increases the expression of VPS34 in Gn pig ileum. Red, VPS34. (C) HRV with/without LGG increases the expression of lysozyme in Gn pig ileum. Red, lysozyme; blue, DAPI (20× magnification, scale bar 100 μm).
Mentions: We next investigated the location of autophagy markers in the pig ileum. In the mock control and LGG only groups, we noticed few p-mTOR-positive cells (Figure 3A). In the HRV-infected intestine, p-mTOR staining was more prevalent. LGG treatment decreased the number of p-mTOR-positive cells in HRV-infected intestine. VPS34 levels were similar to those of p-mTOR; LGG treatment suppressed the number of VPS34-positive cells (Figure 3B). Furthermore, immunostaining showed that lysozyme was increased in ilea from HRV and LGG+HRV pigs compared with mock and LGG only pigs (Figure 3C), which was consistent with the real-time PCR result that rotavirus infection induced high levels of lysozyme mRNA (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