Different expression of dectin-1 and Toll-like receptor 2 in the lungs of different immune status mice infected with Aspergillus fumigatus.
BACKGROUND
Invasive pulmonary aspergillosis (IPA) is a severe and frequently fatal disease in patients receiving treatment with immunosuppressive agents such as cyclophosphamide. Aspergillus fumigatus (A. fumigatus) now is a leading cause of IPA. Dectin-1 and Toll-like receptor 2 (TLR2) are important pattern recognition receptors involved in immune responses to A. fumigatus in vitro. However, the expression of the two receptors during the infection of A. fumigatus in vivo is not completely understood. The effects of cyclophosphamide treatment on the expression of the receptors need to be further studied.


METHODS
We established different immune status in mice models with or without A. fumigatus infection. On days 1, 3 and 5 post inoculation, pulmonary tissues from mice of the different groups were harvested. Dectin-1 and TLR2 mRNA expression in the lungs of the mice were investigated by real-time PCR. The pulmonary fungal burden in the mice with A. fumigatus infection was also evaluated.


RESULTS
In the immunocompetent mice, three days after A. fumigatus inoculation, dectin-1 and TLR2 expression increased markedly compared with the normal control group. Cyclophosphamide inhibited the clearance of pathogens and the expression of dectin-1 with or without A. fumigatus infection in the lungs as well. There was no statistical difference in TLR2 expression between the different immune status groups.


CONCLUSIONS
Our results suggest that in vivo, dectin-1 and TLR2 are activated during the experimental period which would provide a broad range of possibilities for a specific and effective inflammatory response to kill A. fumigatus. Inhibition of dectin-1 expression may be one of the mechanisms of cyclophosphamide in the development of IPA.
Department of Dermatology, Research Center of Medical Mycology, Peking University First Hospital, Beijing 100034, China.
Jian-xun
JX
Yang
Wan
W
Liu
Qiao-yun
QY
Lu
Zhe
Z
Wan
Xiao-hong
XH
Wang
Ruo-yu
RY
Li
D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology / Q000502:physiology*; D003520:Cyclophosphamide / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D037181:Lectins, C-Type; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D000099181:Dectin-1
D003520:Cyclophosphamide; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051195:Toll-Like Receptor 2; D000099181:Dectin-1