Enhanced pulmonary allergic responses to Aspergillus in CCR2(-/-) mice

Allergic responses to Aspergillus species exacerbate asthma and cystic fibr osis, The natural defense against live Aspergillus fumigatus spores or coni dia depends on the recruitment and activation of mononuclear and polymorpho nuclear leukocytes, events that are dependent on chemotactic cytokines, in this study, we explored the relative contribution of the monocyte chemoattr actant protein-1 receptor, CCR2, in the pulmonary response to A, fumigatus conidia, Following sensitization to soluble A, fumigatus Ags, mire larking CCR2 due to targeted deletion were markedly more susceptible to the injurio us effects of an intrapulmonary challenge with live conidia compared with m ice that expressed CCR2 or CCR2(+/+). CCR2(-/-) mice exhibited a major defe ct in the recruitment of polymorphonuclear cells, but these mice also had s ignificantly more eosinophils and lymphocytes in bronchoalveolar lavage sam ples. CCR2(-/)- mice also had significant increases in serum levels of tota l IgE and whole lung levels of IL-5, IL-13, eotaxin, and RANTES compared wi th CCR2(+/+) mice, Airway inflammation, hyper-responsiveness to spasmogens, and subepithelial fibrosis were significantly enhanced in CCR2(-/-) mice c ompared with CCR2(+/+) mice after the conidia challenge. Thus, these findin gs demonstrate that CCR2 plays an important role in the immune response aga inst A. fumigatus, thereby limiting the allergic airway inflammatory and re modeling responses to this fungus.