Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression

J. Saravia, Dahui You, P. Thevenot, G. I. Lee, B. Shrestha, S. Lomnicki, Stephania Cormier

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-lifeCDPMexposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPMHDM failed to develop a typical asthma phenotype including airway hyper-responsiveness, T-helper type 2 (Th2) inflammation, Muc5ac expression, eosinophilia, and HDM-specific immunoglobulin (Ig) compared with HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was twofold higher in CDPMHDM mice compared with HDM mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and regulatory T cells, resulting in the suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life.

Original languageEnglish (US)
Pages (from-to)694-704
Number of pages11
JournalMucosal Immunology
Volume7
Issue number3
DOIs
StatePublished - Jan 1 2014

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Particulate Matter
Immunosuppression
Pyroglyphidae
Asthma
Lung
Immunoglobulin E
Allergens
Respiratory Hypersensitivity
Dermatophagoides Antigens
Inflammation
Eosinophilia
Adaptive Immunity
Regulatory T-Lymphocytes
Immunosuppressive Agents
Child Development
Dendritic Cells
Lung Diseases
Immunoglobulins
Pneumonia
Phenotype

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Saravia, J., You, D., Thevenot, P., Lee, G. I., Shrestha, B., Lomnicki, S., & Cormier, S. (2014). Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression. Mucosal Immunology, 7(3), 694-704. https://doi.org/10.1038/mi.2013.88

Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression. / Saravia, J.; You, Dahui; Thevenot, P.; Lee, G. I.; Shrestha, B.; Lomnicki, S.; Cormier, Stephania.

In: Mucosal Immunology, Vol. 7, No. 3, 01.01.2014, p. 694-704.

Research output: Contribution to journalArticle

Saravia, J, You, D, Thevenot, P, Lee, GI, Shrestha, B, Lomnicki, S & Cormier, S 2014, 'Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression', Mucosal Immunology, vol. 7, no. 3, pp. 694-704. https://doi.org/10.1038/mi.2013.88
Saravia, J. ; You, Dahui ; Thevenot, P. ; Lee, G. I. ; Shrestha, B. ; Lomnicki, S. ; Cormier, Stephania. / Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression. In: Mucosal Immunology. 2014 ; Vol. 7, No. 3. pp. 694-704.
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