title: Cyclophosphamide reduces dectin-1 expression in the lungs of naive and Aspergillus fumigatus-infected mice.
abstract: 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.
authors.affiliation: Department of Dermatology, Research Center of Medical Mycology, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Yang
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Lu
authors.forename: Wan
authors.initials: W
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wan
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001228:Aspergillosis / Q000276:immunology / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000502:physiology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007121:Immunocompetence; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D037181:Lectins, C-Type; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018709:Statistics, Nonparametric; D000099181:Dectin-1
chemical_list: D003520:Cyclophosphamide; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1