title: Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2.
abstract: BACKGROUND
  Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma.
  
  
  METHODS
  To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response.
  
  
  RESULTS
  We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines.
  
  
  CONCLUSIONS
  We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.
authors.affiliation: Lung Biology Center, Department of Medicine, University of California, San Francisco, California, USA. lkoth@itsa.ucsf.edu <lkoth@itsa.ucsf.edu>
authors.forename: Laura L
authors.initials: LL
authors.lastname: Koth
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Rodriguez
authors.forename: Xin Liu
authors.initials: XL
authors.lastname: Bernstein
authors.forename: Salina
authors.initials: S
authors.lastname: Chan
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Huang
authors.forename: Israel F
authors.initials: IF
authors.lastname: Charo
authors.forename: Barrett J
authors.initials: BJ
authors.lastname: Rollins
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004802:Eosinophilia / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005355:Fibrosis / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000946:Antigens, Fungal; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine