Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring

doi:10.1016/j.jaci.2016.12.972

Journal of Allergy and Clinical Immunology

Volume 140, Issue 5, November 2017, Pages 1404-1415.e9

https://doi.org/10.1016/j.jaci.2016.12.972 Get rights and content

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, T_H2-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, T_H2 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.

Section snippets

Methods

For a complete description of the materials and methods used in the murine and in vitro experiments, please see the Methods section in this article's Online Repository at www.jacionline.org

Maternal exposure to HDM allergen exacerbates asthma in offspring

Given that prenatal exposures to environmental stimuli can influence offspring asthma, and HDM sensitization is a powerful risk factor for asthma development, we sought to determine whether maternal exposure to HDM during pregnancy impacted offspring asthma. Female A/J mice (a strain that develops severe AHR associated with a mixed T_H2/T_H17 response43, 44) were exposed to 20 μg HDM extract on days 0, 4, and 10 of pregnancy to ensure a strong HDM-specific immune response was ongoing during

Discussion

Herein, we demonstrate that prenatal exposure to the relevant human aeroallergen, HDM, in the absence of powerful T_H2-skewing adjuvants, is sufficient to exacerbate the development of HDM-driven allergic asthma in offspring later in life. Specifically, offspring of allergen-exposed mothers demonstrated more robust AHR and airway inflammation. The increased phenotypic measures of asthma were associated with a greater capacity for T_H2 cytokine production and frequency of CD4⁺IL-13⁺ cells in the

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: This study was funded by the National Institute of Environmental Health Sciences (grant no. P30 ES006096 to I.P.L.), the National Heart, Lung, and Blood Institute (grant no. R01 HL122300 to I.P.L.), the Cincinnati Children's Hospital Medical Center Perinatal Infection and Inflammation Collaborative (C.A.C. and I.P.L.), and the National Institute of Allergy and Infectious Diseases (grant no. R21 AI119385 to I.P.L.).

: Disclosure of potential conflict of interest: C. A. Chougnet receives grant support from the National Institutes of Health (NIH) and Buroughts-Wellcome and is a section editor for the Journal of Immunology. I. P. Lewkowich receives grant support from the NIH; serves as a consultant for Janssen Pharmaceuticals; and received travel support from Autumn Immunology Conference Executive Council Meeting. The rest of the authors declare that they have no relevant conflicts of interest.

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Environmental and occupational diseaseMaternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring

Background

Objective

Methods

Results

Conclusions

Section snippets

Methods

Maternal exposure to HDM allergen exacerbates asthma in offspring

Discussion

J Allergy Clin Immunol

J Biol Chem

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Am J Pathol

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Immunol Methods

J Immunol Methods

J Allergy Clin Immunol

Am J Pathol

J Allergy Clin Immunol

Childhood asthma epidemiology: insights from comparative studies of rural and urban populations

Pediatr Pulmonol

The asthma epidemic

N Engl J Med

Discovering susceptibility genes for asthma and allergy

Nat Rev Immunol

A large-scale, consortium-based genomewide association study of asthma

N Engl J Med

Variants of DENND1B associated with asthma in children

N Engl J Med

Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children's Respiratory Study

Am J Epidemiol

Environmental and occupational disease
Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring