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S. mansoni bolsters anti-viral immunity in the murine respiratory tract.

Scheer S, Krempl C, Kallfass C, Frey S, Jakob T, Mouahid G, Moné H, Schmitt-Gräff A, Staeheli P, Lamers MC - PLoS ONE (2014)

Bottom Line: The human intestinal parasite Schistosoma mansoni causes a chronic disease, schistosomiasis or bilharzia.The latter cell type is, however, indispensable for anti-viral immune responses.High serum levels of TNF-α, IFN-γ, IL-5, IL-13, IL-2, IL-17, and GM-CSF were found after mating and oviposition.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; International Max Planck Research School of Molecular and Cellular Biology, Freiburg, Germany; University of Freiburg, Freiburg, Germany.

ABSTRACT
The human intestinal parasite Schistosoma mansoni causes a chronic disease, schistosomiasis or bilharzia. According to the current literature, the parasite induces vigorous immune responses that are controlled by Th2 helper cells at the expense of Th1 helper cells. The latter cell type is, however, indispensable for anti-viral immune responses. Remarkably, there is no reliable literature among 230 million patients worldwide describing defective anti-viral immune responses in the upper respiratory tract, for instance against influenza A virus or against respiratory syncitial virus (RSV). We therefore re-examined the immune response to a human isolate of S. mansoni and challenged mice in the chronic phase of schistosomiasis with influenza A virus, or with pneumonia virus of mice (PVM), a mouse virus to model RSV infections. We found that mice with chronic schistosomiasis had significant, systemic immune responses induced by Th1, Th2, and Th17 helper cells. High serum levels of TNF-α, IFN-γ, IL-5, IL-13, IL-2, IL-17, and GM-CSF were found after mating and oviposition. The lungs of diseased mice showed low-grade inflammation, with goblet cell hyperplasia and excessive mucus secretion, which was alleviated by treatment with an anti-TNF-α agent (Etanercept). Mice with chronic schistosomiasis were to a relative, but significant extent protected from a secondary viral respiratory challenge. The protection correlated with the onset of oviposition and TNF-α-mediated goblet cell hyperplasia and mucus secretion, suggesting that these mechanisms are involved in enhanced immune protection to respiratory viruses during chronic murine schistosomiasis. Indeed, also in a model of allergic airway inflammation mice were protected from a viral respiratory challenge with PVM.

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Muc5ac and Muc5b expression in the lungs of mice with chronic schistosomiasis before and after treatment with Etanercept.At 11 week of infection with S. mansoni, mice were treated 3 times, every other day, with 4 mg/kg body weight, intraperitoneally. Lungs were taken at day 6 of treatment. Error bars represent SEM. Significant differences between each time point and control mice (day 0) are marked: *, p≤0.05.
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pone-0112469-g004: Muc5ac and Muc5b expression in the lungs of mice with chronic schistosomiasis before and after treatment with Etanercept.At 11 week of infection with S. mansoni, mice were treated 3 times, every other day, with 4 mg/kg body weight, intraperitoneally. Lungs were taken at day 6 of treatment. Error bars represent SEM. Significant differences between each time point and control mice (day 0) are marked: *, p≤0.05.

Mentions: Goblet cell hyperplasia can be induced, among others, by IL-13 [38] and TNF-α[39], [40]. A hallmark of goblet cell hyperplasia is the increased production of the gel-forming mucin Muc5ac [41], [42]. We determined Muc5ac mRNA levels in lungs of mice infected with S. mansoni and in control mice. Muc5ac mRNA levels were 10× times higher in infected mice compared to control mice. As expected [42], only a moderate induction of the levels of Muc5b was found in infected animals. We treated mice with soluble TNF-receptor (Etanercept) [43] to explore the role of TNF-α in the increased mucus production. After treatment of the mice (starting at week 11 of infection), mRNA for Muc5ac returned to baseline levels (Fig. 4). Thus, we conclude that TNF-α is essential for pulmonary goblet cell hyperplasia in chronic schistosomiasis.


S. mansoni bolsters anti-viral immunity in the murine respiratory tract.

Scheer S, Krempl C, Kallfass C, Frey S, Jakob T, Mouahid G, Moné H, Schmitt-Gräff A, Staeheli P, Lamers MC - PLoS ONE (2014)

Muc5ac and Muc5b expression in the lungs of mice with chronic schistosomiasis before and after treatment with Etanercept.At 11 week of infection with S. mansoni, mice were treated 3 times, every other day, with 4 mg/kg body weight, intraperitoneally. Lungs were taken at day 6 of treatment. Error bars represent SEM. Significant differences between each time point and control mice (day 0) are marked: *, p≤0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4232382&req=5

pone-0112469-g004: Muc5ac and Muc5b expression in the lungs of mice with chronic schistosomiasis before and after treatment with Etanercept.At 11 week of infection with S. mansoni, mice were treated 3 times, every other day, with 4 mg/kg body weight, intraperitoneally. Lungs were taken at day 6 of treatment. Error bars represent SEM. Significant differences between each time point and control mice (day 0) are marked: *, p≤0.05.
Mentions: Goblet cell hyperplasia can be induced, among others, by IL-13 [38] and TNF-α[39], [40]. A hallmark of goblet cell hyperplasia is the increased production of the gel-forming mucin Muc5ac [41], [42]. We determined Muc5ac mRNA levels in lungs of mice infected with S. mansoni and in control mice. Muc5ac mRNA levels were 10× times higher in infected mice compared to control mice. As expected [42], only a moderate induction of the levels of Muc5b was found in infected animals. We treated mice with soluble TNF-receptor (Etanercept) [43] to explore the role of TNF-α in the increased mucus production. After treatment of the mice (starting at week 11 of infection), mRNA for Muc5ac returned to baseline levels (Fig. 4). Thus, we conclude that TNF-α is essential for pulmonary goblet cell hyperplasia in chronic schistosomiasis.

Bottom Line: The human intestinal parasite Schistosoma mansoni causes a chronic disease, schistosomiasis or bilharzia.The latter cell type is, however, indispensable for anti-viral immune responses.High serum levels of TNF-α, IFN-γ, IL-5, IL-13, IL-2, IL-17, and GM-CSF were found after mating and oviposition.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; International Max Planck Research School of Molecular and Cellular Biology, Freiburg, Germany; University of Freiburg, Freiburg, Germany.

ABSTRACT
The human intestinal parasite Schistosoma mansoni causes a chronic disease, schistosomiasis or bilharzia. According to the current literature, the parasite induces vigorous immune responses that are controlled by Th2 helper cells at the expense of Th1 helper cells. The latter cell type is, however, indispensable for anti-viral immune responses. Remarkably, there is no reliable literature among 230 million patients worldwide describing defective anti-viral immune responses in the upper respiratory tract, for instance against influenza A virus or against respiratory syncitial virus (RSV). We therefore re-examined the immune response to a human isolate of S. mansoni and challenged mice in the chronic phase of schistosomiasis with influenza A virus, or with pneumonia virus of mice (PVM), a mouse virus to model RSV infections. We found that mice with chronic schistosomiasis had significant, systemic immune responses induced by Th1, Th2, and Th17 helper cells. High serum levels of TNF-α, IFN-γ, IL-5, IL-13, IL-2, IL-17, and GM-CSF were found after mating and oviposition. The lungs of diseased mice showed low-grade inflammation, with goblet cell hyperplasia and excessive mucus secretion, which was alleviated by treatment with an anti-TNF-α agent (Etanercept). Mice with chronic schistosomiasis were to a relative, but significant extent protected from a secondary viral respiratory challenge. The protection correlated with the onset of oviposition and TNF-α-mediated goblet cell hyperplasia and mucus secretion, suggesting that these mechanisms are involved in enhanced immune protection to respiratory viruses during chronic murine schistosomiasis. Indeed, also in a model of allergic airway inflammation mice were protected from a viral respiratory challenge with PVM.

Show MeSH
Related in: MedlinePlus