title: Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation.
abstract: BACKGROUND
  Schistosomiasis, a chronic helminth infection, elicits distinct immune responses within the host, ranging from an initial TH1 and subsequent TH2 phase to a regulatory state, and is associated with dampened allergic reactions within the host.
  
  
  OBJECTIVE
  We sought to evaluate whether non-transplacental helminth infection during pregnancy alters the offspring's susceptibility to allergy.
  
  
  METHODS
  Ovalbumin-induced allergic airway inflammation was analyzed in offspring from Schistosoma mansoni-infected mothers mated during the TH1, TH2, or regulatory phase of infection. Embryos derived from in vitro fertilized oocytes of acutely infected females were transferred into uninfected foster mice to determine the role of placental environment. The fetomaternal unit was further characterized by helminth-specific immune responses and microarray analyses. Eventually, IFN-γ-deficient mice were infected to evaluate the role of this predominant cytokine on the offspring's allergy phenotype.
  
  
  RESULTS
  We demonstrate that offspring from schistosome-infected mothers that were mated in the TH1 and regulatory phases, but not the TH2 immune phase, are protected against the onset of allergic airway inflammation. Interestingly, these effects were associated with distinctly altered schistosome-specific cytokine and gene expression profiles within the fetomaternal interface. Furthermore, we identified that it is not the transfer of helminth antigens but rather maternally derived IFN-γ during the acute phase of infection that is essential for the progeny's protective immune phenotype.
  
  
  CONCLUSIONS
  Overall, we present a novel immune phase-dependent coherency between the maternal immune responses during schistosomiasis and the progeny's predisposition to allergy. Therefore, we propose to include helminth-mediated transmaternal immune modulation into the expanded hygiene hypothesis.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene (MIH), Technische Universität München, Munich, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Straubinger
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene (MIH), Technische Universität München, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Paul
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene (MIH), Technische Universität München, Munich, Germany.
authors.forename: Olivia
authors.initials: O
authors.lastname: Prazeres da Costa
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene (MIH), Technische Universität München, Munich, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ritter
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene (MIH), Technische Universität München, Munich, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buch
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene (MIH), Technische Universität München, Munich, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Clinic Bonn, Bonn, Germany.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Layland
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene (MIH), Technische Universität München, Munich, Germany. Electronic address: Clarissa.daCosta@tum.de.
authors.forename: Clarissa U
authors.initials: CU
authors.lastname: Prazeres da Costa
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Maternal helminth infection; allergic airway inflammation; hygiene hypothesis; in utero programming; offspring; pregnancy