Phoebe K Richgels1, Amnah Yamani1, Claire A Chougnet1, Ian P Lewkowich2. 1. Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 2. Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Ian.Lewkowich@cchmc.org.
Abstract
BACKGROUND: Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. OBJECTIVE: We sought to determine whether maternal HDM exposure influences asthma development in offspring. METHODS: Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, TH2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. RESULTS: Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, TH2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. CONCLUSIONS: Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma.
BACKGROUND: Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. OBJECTIVE: We sought to determine whether maternal HDM exposure influences asthma development in offspring. METHODS: Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, TH2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. RESULTS: Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, TH2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. CONCLUSIONS: Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma.
Authors: S Hasan Arshad; Wilfried Karmaus; Abid Raza; Ramesh J Kurukulaaratchy; Sharon M Matthews; John W Holloway; Alireza Sadeghnejad; Hongmei Zhang; Graham Roberts; Susan L Ewart Journal: J Allergy Clin Immunol Date: 2012-05-18 Impact factor: 10.793
Authors: R T Stein; C J Holberg; D Sherrill; A L Wright; W J Morgan; L Taussig; F D Martinez Journal: Am J Epidemiol Date: 1999-06-01 Impact factor: 4.897
Authors: J Riedler; C Braun-Fahrländer; W Eder; M Schreuer; M Waser; S Maisch; D Carr; R Schierl; D Nowak; E von Mutius Journal: Lancet Date: 2001-10-06 Impact factor: 79.321
Authors: Tiina Reponen; James Lockey; David I Bernstein; Stephen J Vesper; Linda Levin; Gurjit K Khurana Hershey; Shu Zheng; Patrick Ryan; Sergey A Grinshpun; Manuel Villareal; Grace Lemasters Journal: J Allergy Clin Immunol Date: 2012-07-11 Impact factor: 10.793
Authors: Eric B Brandt; Melinda Butsch Kovacic; Gerald B Lee; Aaron M Gibson; Thomas H Acciani; Timothy D Le Cras; Patrick H Ryan; Alison L Budelsky; Gurjit K Khurana Hershey Journal: J Allergy Clin Immunol Date: 2013-09-20 Impact factor: 10.793
Authors: Katie M Lebold; Matthew G Drake; Alexandra B Pincus; Aubrey B Pierce; Allison D Fryer; David B Jacoby Journal: Am J Respir Cell Mol Biol Date: 2022-07 Impact factor: 7.748
Authors: Katie M Lebold; Matthew G Drake; Lauren B Hales-Beck; Allison D Fryer; David B Jacoby Journal: Am J Respir Cell Mol Biol Date: 2020-04 Impact factor: 6.914
Authors: Carrie V Breton; Remy Landon; Linda G Kahn; Michelle Bosquet Enlow; Alicia K Peterson; Theresa Bastain; Joseph Braun; Sarah S Comstock; Cristiane S Duarte; Alison Hipwell; Hong Ji; Janine M LaSalle; Rachel L Miller; Rashelle Musci; Jonathan Posner; Rebecca Schmidt; Shakira F Suglia; Irene Tung; Daniel Weisenberger; Yeyi Zhu; Rebecca Fry Journal: Commun Biol Date: 2021-06-22