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

PLoS One. 2014 Nov 14;9(11):e112469. doi: 10.1371/journal.pone.0112469. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage
  • Coinfection / immunology*
  • Cytokines / blood
  • Etanercept
  • Flow Cytometry
  • Influenza A virus / immunology*
  • Lung / pathology
  • Mice
  • Mucin 5AC / metabolism
  • Mucin-5B / metabolism
  • Murine pneumonia virus / immunology*
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Schistosoma mansoni / immunology*
  • Schistosomiasis mansoni / immunology*
  • Statistics, Nonparametric
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Cytokines
  • Muc5ac protein, mouse
  • Muc5b protein, mouse
  • Mucin 5AC
  • Mucin-5B
  • Etanercept

Grants and funding

SS was supported by the Fonds National de la Recherche, Luxembourg (http://www.fnr.lu) (PHD-08-045-RE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.