Enhanced Pulmonary Allergic Responses toAspergillusin CCR2−/− Mice
- 1 September 2000
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 165 (5), 2603-2611
- https://doi.org/10.4049/jimmunol.165.5.2603
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.Keywords
This publication has 31 references indexed in Scilit:
- Chronic Airway Hyperreactivity, Goblet Cell Hyperplasia, and Peribronchial Fibrosis during Allergic Airway Disease Induced by Aspergillus fumigatusThe American Journal of Pathology, 2000
- Discussion: Mechanisms of antihistaminesClinical and Experimental Allergy, 1999
- Animal models of asthma and chronic bronchitisClinical and Experimental Allergy, 1999
- Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1JCI Insight, 1999
- Allergic Bronchopulmonary AspergillosisAnnual Review of Medicine, 1999
- Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice.JCI Insight, 1997
- Interleukin-10 Is a Natural Suppressor of Cytokine Production and Inflammation in a Murine Model of Allergic Bronchopulmonary AspergillosisThe Journal of Experimental Medicine, 1997
- Chemokine-leukocyte interactions. The voodoo that they do so wellCytokine & Growth Factor Reviews, 1996
- Asp f I CD4 + TH2-like T-cell lines in allergic bronchopulmonary aspergillosisJournal of Allergy and Clinical Immunology, 1994
- TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional PropertiesAnnual Review of Immunology, 1989