The role of CC chemokine receptor 5 (CCR5) and RANTES/CCL5 during chronic fungal asthma in mice.
In the present study, we explored the role of CC chemokine receptor 5 (CCR5) in a murine model of chronic fungal asthma induced by an intrapulmonary challenge with Aspergillus fumigatus conidia (or spores). Airway hyperresponsiveness was significantly lower in A. fumigatus-sensitized mice lacking CCR5 (CCR5-/-) compared with similarly sensitized wild-type (CCR5+/+) control mice at days 2, 21, 30, and 40 after the conidia challenge. CCR5-/- mice exhibited significantly less peribronchial T-cell and eosinophil accumulation and airway-remodeling features, such as goblet cell hyperplasia and peribronchial fibrosis, compared with CCR5+/+ mice at these times after conidia. However, both groups of mice exhibited similar allergic airway disease at day 12 after the conidia challenge. In CCR5-/- mice at day 12, the allergic airway disease was associated with airway hyperresponsiveness, peribronchial allergic inflammation, and goblet cell hyperplasia. Immunoneutralization of RANTES/CCL5 in sensitized CCR5+/+ and CCR5-/- mice for 12 days after the conidia challenge significantly reduced the peribronchial inflammation and airway hyperresponsiveness in comparison with control wild-type and knockout mice at this time. These data demonstrate that functional CCR5 and RANTES/CCL5 are required for the persistence of chronic fungal asthma in mice.
Schuh
Jane M
JM
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Blease
Kate
K
Hogaboam
Cory M
CM
D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D001232:Aspergillus fumigatus; D001249:Asthma / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D018946:Chemokine CCL5 / Q000378:metabolism*; D002908:Chronic Disease; D005838:Genotype; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D018946:Chemokine CCL5; D019713:Receptors, CCR5