Related Experiment Video
Updated: Aug 11, 2026
A Reversible, Non-invasive Method for Airway Resistance Measurements and Bronchoalveolar Lavage Fluid Sampling in Mice
Published on: April 13, 2010
Enhanced pulmonary allergic responses to Aspergillus in CCR2-/- mice
K Blease1, B Mehrad, T J Standiford
1Department of Pathology, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Abstract:
Allergic responses to Aspergillus species exacerbate asthma and cystic fibrosis. The natural defense against live Aspergillus fumigatus spores or conidia depends on the recruitment and activation of mononuclear and polymorphonuclear leukocytes, events that are dependent on chemotactic cytokines. In this study, we explored the relative contribution of the monocyte chemoattractant protein-1 receptor, CCR2, in the pulmonary response to A. fumigatus conidia. Following sensitization to soluble A. fumigatus Ags, mice lacking CCR2 due to targeted deletion were markedly more susceptible to the injurious effects of an intrapulmonary challenge with live conidia compared with mice that expressed CCR2 or CCR2+/+. CCR2-/- mice exhibited a major defect in the recruitment of polymorphonuclear cells, but these mice also had significantly more eosinophils and lymphocytes in bronchoalveolar lavage samples. CCR2-/- mice also had significant increases in serum levels of total IgE and whole lung levels of IL-5, IL-13, eotaxin, and RANTES compared with CCR2+/+ mice. Airway inflammation, hyper-responsiveness to spasmogens, and subepithelial fibrosis were significantly enhanced in CCR2-/- mice compared with CCR2+/+ mice after the conidia challenge. Thus, these findings demonstrate that CCR2 plays an important role in the immune response against A. fumigatus, thereby limiting the allergic airway inflammatory and remodeling responses to this fungus.
Insights
The monocyte chemoattractant protein-1 receptor, CCR2, limits allergic airway inflammation and lung damage caused by Aspergillus fumigatus. Mice lacking CCR2 showed increased susceptibility and exacerbated allergic responses to fungal spores.
Area of Science:
- Immunology
- Pulmonology
- Microbiology
Background:
- Allergic responses to Aspergillus species worsen asthma and cystic fibrosis.
- Immune defense against Aspergillus fumigatus spores relies on leukocyte recruitment, mediated by chemotactic cytokines.
- The role of the monocyte chemoattractant protein-1 receptor (CCR2) in pulmonary responses to Aspergillus fumigatus is not fully understood.
Purpose of the Study:
- To investigate the contribution of CCR2 to the pulmonary immune response following Aspergillus fumigatus conidia challenge.
- To determine how CCR2 deficiency impacts allergic airway inflammation and lung remodeling.
Main Methods:
- Mice were sensitized to soluble Aspergillus fumigatus antigens.
- CCR2-deficient (CCR2-/-) and wild-type (CCR2+/+) mice were challenged with live Aspergillus fumigatus conidia.
- Pulmonary immune cell infiltration, serum IgE levels, and lung cytokine expression were analyzed.
- Airway inflammation, hyper-responsiveness, and subepithelial fibrosis were assessed.
Main Results:
- CCR2-/- mice were more susceptible to Aspergillus fumigatus conidia challenge, exhibiting increased lung injury.
- A defect in polymorphonuclear cell recruitment was observed in CCR2-/- mice, alongside increased eosinophils and lymphocytes.
- CCR2-/- mice showed elevated serum total IgE and lung levels of IL-5, IL-13, eotaxin, and RANTES.
- Airway inflammation, hyper-responsiveness, and subepithelial fibrosis were significantly enhanced in CCR2-/- mice.
Conclusions:
- CCR2 plays a critical role in the immune response against Aspergillus fumigatus.
- CCR2 limits allergic airway inflammation and fungal-induced lung remodeling.
- Targeting CCR2 may offer therapeutic potential for Aspergillus-related respiratory diseases.
