Evidence for the involvement of cofilin in Aspergillus fumigatus internalization into type II alveolar epithelial cells.
BACKGROUND
The internalization of Aspergillus fumigatus into alveolar epithelial cells (AECs) is tightly controlled by host cellular actin dynamics, which require close modulation of the ADF (actin depolymerizing factor)/cofilin family. However, the role of cofilin in A. fumigatus internalization into AECs remains unclear.


RESULTS
Here, we demonstrated that germinated A. fumigatus conidia were able to induce phosphorylation of cofilin in A549 cells during the early stage of internalization. The modulation of cofilin activity by overexpression, knockdown, or mutation of the cofilin gene in A549 cells decreased the efficacy of A. fumigatus internalization. Reducing the phosphorylation status of cofilin with BMS-5 (LIM kinase inhibitor) or overexpression of the slingshot phosphatases also impeded A. fumigatus internalization. Both the C. botulimun C3 transferase (a specific RhoA inhibitor) and Y27632 (a specific ROCK inhibitor) reduced the internalization of A. fumigatus and the level of phosphorylated cofilin. β-1,3-glucan (the major component of the conidial cell wall) and its host cell receptor dectin-1 did not seem to be associated with cofilin phosphorylation during A. fumigatus infection.


CONCLUSIONS
These results indicated that cofilin might be involved in the modulation of A. fumigatus internalization into type II alveolar epithelial cells through the RhoA-ROCK-LIM kinase pathway.
Department of Respiratory Medicine, Shanghai first people's hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China. baojiangu0514@126.com.|Department of Respiratory Medicine, Ruijin hospital, School of Medicine, Shanghai Jiaotong University, No. 197 Ruijin Er Road, Shanghai, 200025, China. baojiangu0514@126.com.
Zhiyao
Z
Bao
Department for Hospital Infection Control & Research, Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Fengtai Dong Street 20, Beijing, 100071, China. yilin791228@126.com.
Xuelin
X
Han
Department for Hospital Infection Control & Research, Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Fengtai Dong Street 20, Beijing, 100071, China. chenfangyan1986@163.com.
Fangyan
F
Chen
Department for Hospital Infection Control & Research, Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Fengtai Dong Street 20, Beijing, 100071, China. feixiang.5420@163.com.
Xiaodong
X
Jia
Department for Hospital Infection Control & Research, Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Fengtai Dong Street 20, Beijing, 100071, China. mniss2011@163.com.
Jingya
J
Zhao
Department for Hospital Infection Control & Research, Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Fengtai Dong Street 20, Beijing, 100071, China. sdupdf@163.com.
Changjian
C
Zhang
Department for Hospital Infection Control & Research, Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Fengtai Dong Street 20, Beijing, 100071, China. chenyonger@126.com.
Chen
C
Yong
Department for Hospital Infection Control & Research, Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Fengtai Dong Street 20, Beijing, 100071, China. shuguangcdc@163.com.
Shuguang
S
Tian
Department of Respiratory Medicine, Shanghai first people's hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China. xzhou53@163.com.
Xin
X
Zhou
Department for Hospital Infection Control & Research, Institute of Disease Control & Prevention of PLA, Academy of Military Medical Sciences, Fengtai Dong Street 20, Beijing, 100071, China. hanlicdc@163.com.
Li
L
Han
D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000502:physiology*; D002460:Cell Line; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans
D051339:Actin Depolymerizing Factors