S. mansoni bolsters anti-viral immunity in the murine respiratory tract.
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.
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.
Sebastian
S
Scheer
Institute of Virology and Immunology, University of Wuerzburg, Wuerzburg, Germany.
Christine
C
Krempl
Institute for Virology, Department of Medical Microbiology and Hygiene, University Medical Center Freiburg, Freiburg, Germany.
Carsten
C
Kallfass
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany.
Stefanie
S
Frey
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany.
Thilo
T
Jakob
Univ. Perpignan Via Domitia, Ecologie et Evolution des Interactions, UMR 5244, F-66860, Perpignan, France.
Gabriel
G
Mouahid
CNRS, Ecologie et Evolution des Interactions, UMR 5244, F-66860, Perpignan, France.
Hélène
H
Moné
Institute of Pathology, University of Freiburg, Freiburg, Germany.
Annette
A
Schmitt-Gräff
Institute for Virology, Department of Medical Microbiology and Hygiene, University Medical Center Freiburg, Freiburg, Germany.
Peter
P
Staeheli
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Marinus C
MC
Lamers
D000818:Animals; D018893:Bronchoalveolar Lavage; D060085:Coinfection / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D000068800:Etanercept; D005434:Flow Cytometry; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000473:pathology; D051379:Mice; D055271:Mucin 5AC / Q000378:metabolism; D055257:Mucin-5B / Q000378:metabolism; D029122:Murine pneumonia virus / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018709:Statistics, Nonparametric; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines; C524679:Muc5ac protein, mouse; C524579:Muc5b protein, mouse; D055271:Mucin 5AC; D055257:Mucin-5B; D000068800:Etanercept