PhD defence X. Han

Internalization of Aspergillus fumigatus into pulmonary epithelial cells: joint action of host and pathogen

The thesis of Xuelin Han provides new important clues to understand the pathogenic mechanisms of Aspergillus (A.). fumigatus invasion and responses in the host. A. fumigatus is a very important opportunistic fungus. It causes about 90% of the systemic infections due to Aspergillus. The primary site of infection is the lung. The process of A. fumigatus internalization into pulmonary epithelial cells is a key step in the cause of aspergillosis. Pulmonary epithelial cells act not only as mechanical barrier but also as first defense line of the host innate immune system. But until now the mechanisms leading to the internalization of A. fumigatus into pulmonary epithelial cells are largely unknown. In her thesis Han studied a subset of molecules and signaling pathways involved in this process from both A. fumigatus and the host. Hanfound that β-1,3-glucan and gliotoxin, factors from A. fumigatus, increase the internalization of A. fumigatus into pulmonary epithelial A549 cells by inducing host cellular phospholipase D (PLD) activation. In addition, PLD of A. fumigatus itself is a virulence factor and improves internalization. The thesis also reveals that the phosphorylation status of the actin regulator cofilin in the host determines internalization. DHN-melanin, another main component of A. fumigatus, regulates the level of host cell cyclic AMP and the expression of its downstream molecule Epac. Finally, Han provides important insight into dynamic transcriptome profiles in A549 cells during A. fumigatus infection by using RNA-Seq technology.

Dissertation

Promotores: Prof.dr. M. Schmidt en Prof.dr. L. Han