Aspergillus fumigatus is an important opportunistic fungal pathogen. Patients treated with chemotherapeutic agent such as cyclophosphamide are susceptible to invasive pulmonary aspergillosis. Dectin-1 is a pattern recognition receptor critically involved in immune responses to A. fumigatus. Therefore, we tested whether cyclophosphamide treatment could cause alterations in dectin-1 expression in the lung, which could contribute to invasive pulmonary Aspergillus infections in patients. We established a murine A. fumigatus infectious model to investigate the kinetics of dectin-1 expression in lung tissues in the presence or absence of cyclophosphamide treatment. During infection, dectin-1 expression was strikingly increased in immunocompetent mice infected with A. fumigatus as compared to those in a non-infected control group. In vitro macrophages stimulated with heat-inactivated A. fumigatus conidia expressed a significantly elevated level of dectin-1. Infected mice treated with cyclophosphamide showed decreased levels of dectin-1 and a higher fungal burden in the lung than the infected mice without cyclophosphamide treatment. These results suggest that dectin-1 is involved in host defense against A. fumigatus infection and that suppression of dectin-1 expression caused by cyclophosphamide may contribute to susceptibility to infections caused by this fungus in the immunocompromised host.