title: β-1,3-Glucan-induced host phospholipase D activation is involved in Aspergillus fumigatus internalization into type II human pneumocyte A549 cells.
abstract: The internalization of Aspergillus fumigatus into lung epithelial cells is a process that depends on host cell actin dynamics. The host membrane phosphatidylcholine cleavage driven by phospholipase D (PLD) is closely related to cellular actin dynamics. However, little is known about the impact of PLD on A. fumigatus internalization into lung epithelial cells. Here, we report that once germinated, A. fumigatus conidia were able to stimulate host PLD activity and internalize more efficiently in A549 cells without altering PLD expression. The internalization of A. fumigatus in A549 cells was suppressed by the downregulation of host cell PLD using chemical inhibitors or siRNA interference. The heat-killed swollen conidia, but not the resting conidia, were able to activate host PLD. Further, β-1,3-glucan, the core component of the conidial cell wall, stimulated host PLD activity. This PLD activation and conidia internalization were inhibited by anti-dectin-1 antibody. Indeed, dectin-1, a β-1,3-glucan receptor, was expressed in A549 cells, and its expression profile was not altered by conidial stimulation. Finally, host cell PLD1 and PLD2 accompanied A. fumigatus conidia during internalization. Our data indicate that host cell PLD activity induced by β-1,3-glucan on the surface of germinated conidia is important for the efficient internalization of A. fumigatus into A549 lung epithelial cells.
authors.affiliation: Department for Hospital Infection Control and Research, Institute of Disease Control and Prevention of PLA, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Han
authors.forename: Rentao
authors.initials: R
authors.lastname: Yu
authors.forename: Dongyu
authors.initials: D
authors.lastname: Zhen
authors.forename: Sha
authors.initials: S
authors.lastname: Tao
authors.forename: Martina
authors.initials: M
authors.lastname: Schmidt
authors.forename: Li
authors.initials: L
authors.lastname: Han
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D004705:Endocytosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020868:Gene Silencing / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013172:Spores, Fungal / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity; D047071:beta-Glucans / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D047071:beta-Glucans; C033363:beta-1,3-glucan; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1