CXCR2 is necessary for the development and persistence of chronic fungal asthma in mice.
The role of CXCR during allergic airway and asthmatic diseases is yet to be fully characterized. Therefore, the present study addressed the role of CXCR2 during Aspergillus fumigatus-induced asthma. Mice deficient in CXCR2 (CXCR2-/-) and wild-type counterparts (CXCR2+/+) were sensitized to A. fumigatus Ags and challenged with A. fumigatus conidia, and the resulting allergic airway disease was monitored for up to 37 days. At days 3 and 7 after conidia, CXCR2-/- mice exhibited significantly greater methacholine-induced airway hyperreactivity than did CXCR2+/+ mice. In contrast, CXCR2-deficient mice exhibited significantly less airway hyperresponsiveness than the wild-type control groups at days 14 and 37 after conidia. At all times after conidia, whole lung levels of IL-4, IL-5, and eotaxin/CC chemokine ligand 11 were significantly lower in CXCR2-/- mice than in the wild-type controls. Eosinophil and T cell, but not neutrophil, recruitment into the airways of A. fumigatus-sensitized CXCR2-/- mice was significantly impaired compared with wild-type controls at all times after the conidia challenge. Whole lung levels of IFN-gamma, inflammatory protein-10/CXC ligand (CXCL) 10, and monokine induced by IFN-gamma (MIG)/CXCL9 were significantly increased in CXCR2-/- mice compared with CXCR2+/+ mice at various times after conidia. Interestingly, at day 3 after conidia, neutrophil recruitment and airway hyperresponsiveness in CXCR2-/- mice was mediated by inflammatory protein-10/CXCL10 and, to a lesser degree, MIG/CXCL9. Taken together, these data suggest that CXCR2 contributes to the persistence of asthmatic disease due to A. fumigatus.
Schuh
Jane M
JM
Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109-0602, USA.
Blease
Kate
K
Hogaboam
Cory M
CM
D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000472:pathogenicity; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002465:Cell Movement / Q000276:immunology; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000502:physiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000502:physiology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013172:Spores, Fungal / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000473:pathology
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D015848:Interleukin-5; D019402:Macrophage Inflammatory Proteins; D023063:Receptors, Interleukin-8B; D016210:Methacholine Chloride; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D009195:Peroxidase