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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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Coinfection experiments with S. mansoni-infected C57BL/6J mice and pneumonia virus of mice (PVM).A, Relative weight loss of mice with chronic schistosomiasis (12 wks) and control animals at indicated times after a sublethal dose (200 pfu/mouse) of PVM. Data are from 30–38 mice in 7–8 experiments. B, Relative weight loss of mice at the indicated time points after challenge with 200 pfu/mouse of PVM, at 1 and 4 weeks after infection with S. mansoni. The data are cumulative from 15 (week 1), 6 (week 4), and 52 (control) mice representative of 3, 1 and 12 experiments, respectively; C, Relative weight loss of mice with chronic schistosomiasis (12 weeks) and control animals at indicated time points after a lethal dose (2000 pfu/mouse) of PVM. The data are cumulative from 10 mice in 2 individual experiments; D, Survival curves of mice in Fig. 7C; E, Viral load, expressed as pfu, in the right lobes of the lungs of mice, treated as described in Fig. 7A, at day 4, 7 and 10 after challenge with PVM. Bars represent data from 9–15 mice in 2–4 individual experiments; F, Lungs of mice as described in Fig. 7A were taken at day 4, fixed with paraformaldehyde and stained with an antibody directed against the G-protein of PVM. The infected areas are enclosed with dashed lines. Images are representative for 6 sections from 3 individual mice per group; Error bars represent SEM. Significant differences between groups at one time point are marked: *, p≤0.05; **, p≤0.01; ***, p≤0.001, nd: below detection limit.
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pone-0112469-g007: Coinfection experiments with S. mansoni-infected C57BL/6J mice and pneumonia virus of mice (PVM).A, Relative weight loss of mice with chronic schistosomiasis (12 wks) and control animals at indicated times after a sublethal dose (200 pfu/mouse) of PVM. Data are from 30–38 mice in 7–8 experiments. B, Relative weight loss of mice at the indicated time points after challenge with 200 pfu/mouse of PVM, at 1 and 4 weeks after infection with S. mansoni. The data are cumulative from 15 (week 1), 6 (week 4), and 52 (control) mice representative of 3, 1 and 12 experiments, respectively; C, Relative weight loss of mice with chronic schistosomiasis (12 weeks) and control animals at indicated time points after a lethal dose (2000 pfu/mouse) of PVM. The data are cumulative from 10 mice in 2 individual experiments; D, Survival curves of mice in Fig. 7C; E, Viral load, expressed as pfu, in the right lobes of the lungs of mice, treated as described in Fig. 7A, at day 4, 7 and 10 after challenge with PVM. Bars represent data from 9–15 mice in 2–4 individual experiments; F, Lungs of mice as described in Fig. 7A were taken at day 4, fixed with paraformaldehyde and stained with an antibody directed against the G-protein of PVM. The infected areas are enclosed with dashed lines. Images are representative for 6 sections from 3 individual mice per group; Error bars represent SEM. Significant differences between groups at one time point are marked: *, p≤0.05; **, p≤0.01; ***, p≤0.001, nd: below detection limit.

Mentions: We also performed coinfection experiments with S. mansoni-infected mice and the respiratory virus PVM to validate our findings with a second pneumoviral infection. 12 weeks after infection with S. mansoni, mice were challenged intranasally with a sublethal dose (200 pfu/mouse) of PVM. C57BL/6 mice without S. mansoni showed, as expected [47], signs of disease and a significant loss of weight 8–9 days after infection, followed by a recovery. In contrast, mice infected with S. mansoni 12 weeks before viral challenge did not show additional signs of disease and did not lose weight (Fig. 7A). Viral challenge shortly after infection with S. mansoni did not cause protection (Fig. 7B), in fact, reproducible protection was only found after week 8 of infection (data not shown). Whereas viral challenge with 2000 pfu/mouse was lethal in control mice, mice with chronic (12 weeks) schistosomiasis survived this type of challenge, but they did show signs of disease (Fig. 7C,D). Sublethally infected T cell-deficient mice fail to clear the virus, but they are able to exert some virus control, and the virus load can stay constant over weeks without extensive disease or weight loss [47]. The reported dominant Th2 response and immune regulatory activity in the chronic phase of schistosomiasis prompted the question, whether mice with schistosomiasis controlled or cleared the virus. Fig. 7E shows that mice with schistosomiasis carried a significantly reduced (p≤0.01) viral burden at day 7 post PVM infection and were able to clear the infection. Immunohistochemical staining of the lungs corroborated this finding (Fig. 7F).


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)

Coinfection experiments with S. mansoni-infected C57BL/6J mice and pneumonia virus of mice (PVM).A, Relative weight loss of mice with chronic schistosomiasis (12 wks) and control animals at indicated times after a sublethal dose (200 pfu/mouse) of PVM. Data are from 30–38 mice in 7–8 experiments. B, Relative weight loss of mice at the indicated time points after challenge with 200 pfu/mouse of PVM, at 1 and 4 weeks after infection with S. mansoni. The data are cumulative from 15 (week 1), 6 (week 4), and 52 (control) mice representative of 3, 1 and 12 experiments, respectively; C, Relative weight loss of mice with chronic schistosomiasis (12 weeks) and control animals at indicated time points after a lethal dose (2000 pfu/mouse) of PVM. The data are cumulative from 10 mice in 2 individual experiments; D, Survival curves of mice in Fig. 7C; E, Viral load, expressed as pfu, in the right lobes of the lungs of mice, treated as described in Fig. 7A, at day 4, 7 and 10 after challenge with PVM. Bars represent data from 9–15 mice in 2–4 individual experiments; F, Lungs of mice as described in Fig. 7A were taken at day 4, fixed with paraformaldehyde and stained with an antibody directed against the G-protein of PVM. The infected areas are enclosed with dashed lines. Images are representative for 6 sections from 3 individual mice per group; Error bars represent SEM. Significant differences between groups at one time point are marked: *, p≤0.05; **, p≤0.01; ***, p≤0.001, nd: below detection limit.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0112469-g007: Coinfection experiments with S. mansoni-infected C57BL/6J mice and pneumonia virus of mice (PVM).A, Relative weight loss of mice with chronic schistosomiasis (12 wks) and control animals at indicated times after a sublethal dose (200 pfu/mouse) of PVM. Data are from 30–38 mice in 7–8 experiments. B, Relative weight loss of mice at the indicated time points after challenge with 200 pfu/mouse of PVM, at 1 and 4 weeks after infection with S. mansoni. The data are cumulative from 15 (week 1), 6 (week 4), and 52 (control) mice representative of 3, 1 and 12 experiments, respectively; C, Relative weight loss of mice with chronic schistosomiasis (12 weeks) and control animals at indicated time points after a lethal dose (2000 pfu/mouse) of PVM. The data are cumulative from 10 mice in 2 individual experiments; D, Survival curves of mice in Fig. 7C; E, Viral load, expressed as pfu, in the right lobes of the lungs of mice, treated as described in Fig. 7A, at day 4, 7 and 10 after challenge with PVM. Bars represent data from 9–15 mice in 2–4 individual experiments; F, Lungs of mice as described in Fig. 7A were taken at day 4, fixed with paraformaldehyde and stained with an antibody directed against the G-protein of PVM. The infected areas are enclosed with dashed lines. Images are representative for 6 sections from 3 individual mice per group; Error bars represent SEM. Significant differences between groups at one time point are marked: *, p≤0.05; **, p≤0.01; ***, p≤0.001, nd: below detection limit.
Mentions: We also performed coinfection experiments with S. mansoni-infected mice and the respiratory virus PVM to validate our findings with a second pneumoviral infection. 12 weeks after infection with S. mansoni, mice were challenged intranasally with a sublethal dose (200 pfu/mouse) of PVM. C57BL/6 mice without S. mansoni showed, as expected [47], signs of disease and a significant loss of weight 8–9 days after infection, followed by a recovery. In contrast, mice infected with S. mansoni 12 weeks before viral challenge did not show additional signs of disease and did not lose weight (Fig. 7A). Viral challenge shortly after infection with S. mansoni did not cause protection (Fig. 7B), in fact, reproducible protection was only found after week 8 of infection (data not shown). Whereas viral challenge with 2000 pfu/mouse was lethal in control mice, mice with chronic (12 weeks) schistosomiasis survived this type of challenge, but they did show signs of disease (Fig. 7C,D). Sublethally infected T cell-deficient mice fail to clear the virus, but they are able to exert some virus control, and the virus load can stay constant over weeks without extensive disease or weight loss [47]. The reported dominant Th2 response and immune regulatory activity in the chronic phase of schistosomiasis prompted the question, whether mice with schistosomiasis controlled or cleared the virus. Fig. 7E shows that mice with schistosomiasis carried a significantly reduced (p≤0.01) viral burden at day 7 post PVM infection and were able to clear the infection. Immunohistochemical staining of the lungs corroborated this finding (Fig. 7F).

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