Cyclophosphamide reduces dectin-1 expression in the lungs of naive and Aspergillus fumigatus-infected mice.
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.
Yang
Jianxun
J
Department of Dermatology, Research Center of Medical Mycology, Peking University First Hospital, Peking University, Beijing, China.
Lu
Qiaoyun
Q
Liu
Wan
W
Wan
Zhe
Z
Wang
Xiaohong
X
Li
Ruoyu
R
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
D003520:Cyclophosphamide; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1