Reversible control by vitamin D of granulocytes and bacteria in the lungs of mice: an ovalbumin-induced model of allergic airway disease

PLoS One. 2013 Jun 24;8(6):e67823. doi: 10.1371/journal.pone.0067823. Print 2013.

Abstract

Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D deficiency and asthma has yet to be established. We have developed a 'low dose' model of allergic airway disease induced by intraperitoneal injection with ovalbumin (1 µg) and aluminium hydroxide (0.2 mg) in which characteristics of atopic asthma are recapitulated, including airway hyperresponsiveness, antigen-specific immunoglobulin type-E and lung inflammation. We assessed the effects of vitamin D deficiency throughout life (from conception until adulthood) on the severity of ovalbumin-induced allergic airway disease in vitamin D-replete and -deficient BALB/c mice using this model. Vitamin D had protective effects such that deficiency significantly enhanced eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male but not female mice. Vitamin D also suppressed the proliferation and T helper cell type-2 cytokine-secreting capacity of airway-draining lymph node cells from both male and female mice. Supplementation of initially vitamin D-deficient mice with vitamin D for four weeks returned serum 25-hydroxyvitamin D to levels observed in initially vitamin D-replete mice, and also suppressed eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male mice. Using generic 16 S rRNA primers, increased bacterial levels were detected in the lungs of initially vitamin D-deficient male mice, which were also reduced by vitamin D supplementation. These results indicate that vitamin D controls granulocyte levels in the bronchoalveolar lavage fluid in an allergen-sensitive manner, and may contribute towards the severity of asthma in a gender-specific fashion through regulation of respiratory bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols
  • Allergens / immunology
  • Animals
  • Asthma / immunology
  • Asthma / microbiology
  • Asthma / pathology*
  • Asthma / physiopathology
  • Bacteria / drug effects*
  • Bacterial Load / drug effects
  • Bronchial Hyperreactivity / complications
  • Bronchial Hyperreactivity / pathology
  • Bronchial Hyperreactivity / physiopathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Female
  • Granulocytes / drug effects
  • Granulocytes / metabolism*
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / metabolism
  • Leukocyte Count
  • Lung / drug effects
  • Lung / microbiology*
  • Lung / pathology*
  • Lung / physiopathology
  • Lymph Nodes / drug effects
  • Lymph Nodes / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Vitamin D / pharmacology*
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / microbiology
  • Vitamin D Deficiency / pathology
  • Vitamin D Deficiency / physiopathology

Substances

  • Aerosols
  • Allergens
  • Immunoglobulin G
  • RNA, Messenger
  • Vitamin D
  • Immunoglobulin E
  • Ovalbumin

Grants and funding

This work was supported by the National Health and Medical Research Council of Australia (#458612, PHH, SG; http://www.nhmrc.gov.au), the Cancer Council of Western Australia (#1008985, PHH, SG; http://www.cancerwa.asn.au), the Asthma Foundation of Western Australia (SG, PHH; www.asthmawa.org.au), the Raine Medical Research Foundation (SG, PHH; http://www.raine.uwa.edu.au) and the BrightSpark Foundation (SG; http://www.brightsparkfoundation.com.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.