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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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Serum cytokine levels of C57BL/6J mice infected with S. mansoni.Cytokine levels were determined at indicated time points after infection. The data points represent means from 4–10 mice. Error bars represent SEM. Significant differences between each time point and control mice (day 0) are marked: *, p≤0.05; **, p≤0.01; ***, p≤0.001.
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pone-0112469-g001: Serum cytokine levels of C57BL/6J mice infected with S. mansoni.Cytokine levels were determined at indicated time points after infection. The data points represent means from 4–10 mice. Error bars represent SEM. Significant differences between each time point and control mice (day 0) are marked: *, p≤0.05; **, p≤0.01; ***, p≤0.001.

Mentions: In our studies we used a recent human isolate of S. mansoni, which originated from Oman [22], [29]. We first established the optimal number of cercariae that caused chronic schistosomiasis in C57Bl/6 mice (Fig. S1). 70–75 cercariae per mouse, infected at 9–10 weeks of age, was considered optimal. Herewith a moderate, chronic course of the disease was established that resembled Henderson's moderate splenomegaly syndrome (MSS) of mouse schistosomiasis [30], and that allowed the study of secondary infections in the chronic phase of the disease. Survival at 16 weeks of age was more than 95% in a large group of animals that were infected at different time points during this study. Serum cytokine profiles were also established. As expected, a slight increase in IFN-γ levels was seen immediately after infection, indicative of Th1-type immune responsiveness. Significant Th2-type responsiveness was seen from week 7 of infection onwards, after the onset of oviposition, with IL-4 and IL-5 rising ahead of IL-13. Also, IL-17 and IL-2 levels rose significantly after week 7. We found very high systemic levels of the proinflammatory cytokines IFN-γ, TNF-α and GM-CSF after week 7, which challenges the idea of mutually exclusive immune responses (Fig. 1). IL-10 showed small peaks of activity at week 1, 4, and 8, which most likely reflected a reaction to inflammatory processes after skin and lung passage of the schistosomula, and egg passage into the gut [31].


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)

Serum cytokine levels of C57BL/6J mice infected with S. mansoni.Cytokine levels were determined at indicated time points after infection. The data points represent means from 4–10 mice. Error bars represent SEM. Significant differences between each time point and control mice (day 0) are marked: *, p≤0.05; **, p≤0.01; ***, p≤0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0112469-g001: Serum cytokine levels of C57BL/6J mice infected with S. mansoni.Cytokine levels were determined at indicated time points after infection. The data points represent means from 4–10 mice. Error bars represent SEM. Significant differences between each time point and control mice (day 0) are marked: *, p≤0.05; **, p≤0.01; ***, p≤0.001.
Mentions: In our studies we used a recent human isolate of S. mansoni, which originated from Oman [22], [29]. We first established the optimal number of cercariae that caused chronic schistosomiasis in C57Bl/6 mice (Fig. S1). 70–75 cercariae per mouse, infected at 9–10 weeks of age, was considered optimal. Herewith a moderate, chronic course of the disease was established that resembled Henderson's moderate splenomegaly syndrome (MSS) of mouse schistosomiasis [30], and that allowed the study of secondary infections in the chronic phase of the disease. Survival at 16 weeks of age was more than 95% in a large group of animals that were infected at different time points during this study. Serum cytokine profiles were also established. As expected, a slight increase in IFN-γ levels was seen immediately after infection, indicative of Th1-type immune responsiveness. Significant Th2-type responsiveness was seen from week 7 of infection onwards, after the onset of oviposition, with IL-4 and IL-5 rising ahead of IL-13. Also, IL-17 and IL-2 levels rose significantly after week 7. We found very high systemic levels of the proinflammatory cytokines IFN-γ, TNF-α and GM-CSF after week 7, which challenges the idea of mutually exclusive immune responses (Fig. 1). IL-10 showed small peaks of activity at week 1, 4, and 8, which most likely reflected a reaction to inflammatory processes after skin and lung passage of the schistosomula, and egg passage into the gut [31].

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