Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation

• Published in: Journal of allergy and clinical immunology Vol. 134; no. 6; pp. 1271 - 1279.e10
• Main Authors: Straubinger, Kathrin, PhD, Paul, Sabine, VTA, Prazeres da Costa, Olivia, MSc, Ritter, Manuel, PhD, Buch, Thorsten, PhD, Busch, Dirk H., MD, Layland, Laura E., PhD, Prazeres da Costa, Clarissa U., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-2014; Elsevier; Elsevier Limited
• Subjects: Allergens - immunology; allergic airway inflammation; Allergy and Immunology; Androgens; Animals; Animals, Newborn; Antigens; Arrays; Biological and medical sciences; Biosynthesis; Cytokines - genetics; Cytokines - immunology; Diabetes; Disease Susceptibility - immunology; Epidemiology. Vaccinations; Female; Females; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; General aspects; Heparan sulfate; hygiene hypothesis; Immune system; Immunoglobulin E - immunology; Immunopathology; in utero programming; Infections; Infectious diseases; Maternal helminth infection; Medical sciences; Metabolism; Mice, Inbred BALB C; Mice, Transgenic; offspring; Ovalbumin - immunology; Placenta; Pneumonia - immunology; Pregnancy; Pregnancy - immunology; Respiratory Hypersensitivity - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Schistosoma; Schistosomiasis mansoni - immunology; Serotonin; offspring; Ovalbumin; PAS; hygiene hypothesis; Maternal helminth infection; pregnancy; Treg; AAI; Intracellular cytokine staining; Soluble egg antigen; allergic airway inflammation; BAL; SEA; in utero programming; Aluminium hydroxide (Al[OH] 3); Bronchoalveolar lavage; Reg; Periodic acid–Schiff; ICS; Regulatory T; OVA; Regulatory state; Alum; Allergy; Immunopathology; Immune response; Programming; Inflammation; Parasitosis; Respiratory system; Helminthiasis; In utero; Hypothesis; Infection; Pregnancy; Respiratory tract; Progeny; Sensitivity; Immunology; Mother; Female; Hygiene
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2014.05.034

Background Schistosomiasis, a chronic helminth infection, elicits distinct immune responses within the host, ranging from an initial TH 1 and subsequent TH 2 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 TH 1, TH 2, 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 TH 1 and regulatory phases, but not the TH 2 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. Conclusion 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.