Ambient particulate matter enhances the pulmonary allergic immune response to house dust mite in a BALB/c mouse model by augmenting Th2- and Th17-immune responses

Alejandro R. Castañeda, Christoph F.A. Vogel, Keith J. Bein, Heather K. Hughes, Suzette Smiley-Jewell, Kent E Pinkerton

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Ambient particulate matter (PM) exacerbates airway inflammation and hyper-reactivity in asthmatic patients. Studies show that PM has adjuvant-like properties that enhance the allergic inflammatory response; however, the mechanisms through which PM enhances these processes remain elusive. The objective of the study was to examine how ambient PM enhances the allergic immune response. Eight-week-old BALB/c mice were sensitized with house dust mite (HDM) or HDM and ambient particulate matter (PM, 2.5 μm; Sacramento, CA) to assess how PM modulates the development of adaptive immune responses against allergens. Both groups were challenged with HDM only. Bronchoalveolar lavage (BAL) was analyzed for extent of airway inflammation. Lung tissue was used for histological analysis, mucosubstance quantification, and heme oxygenase-1 (HO-1) localization/quantification. Gene expression was analyzed in whole lung to characterize immune markers of inflammation: cytokines, chemokines, antioxidant enzymes, and transcription factors. Cytokine and chemokine protein levels were quantified in whole lung to confirm gene expression patterns. Compared to HDM-only sensitization, exposure to PM during HDM sensitization led to significant immune cell recruitment into the airway subepithelium, IgE gene expression, mucosubstance production, and Th2-associated cytokine expression. HO-1 levels were not significantly different between the treatment groups. Gene expression profiles suggest that polycyclic aromatic hydrocarbon (PAH) content in PM activated the aryl hydrocarbon receptor (AhR) and enhanced Th17-responses in the mice that received HDM and PM compared to mice that received HDM-only. The findings suggest that PM enhances allergic sensitization via enhancement of Th2-mediated inflammation and that AhR activation by PAHs in PM promotes Th17-immune responses.

Original languageEnglish (US)
Article numbere13827
JournalPhysiological Reports
Volume6
Issue number18
DOIs
StatePublished - Sep 1 2018

Keywords

  • Allergic airway inflammation
  • allergy
  • house dust mite allergen
  • particulate matter
  • Th17 immunity
  • Th2 immunity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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