Figure 8

Proposed model for the involvement of LAMMER kinase in the interaction between A. fumigatus and immune cells. The composition of the cell wall continuously changes during the life cycle of A. fumigatus. The resting conidia first come into contact with host epithelial cells. When conidia swell, the outer layer (melanin and hydrophobins) is removed, uncovering the inner cell wall, which is mainly composed of glucan, chitin, and GM. LkhA regulates the transcription of genes for cell wall components and hydrophobins, which affects PAMP-PRR interactions in alveolar macrophages. This interaction mediates ERK signaling and stimulates the production of the proinflammatory cytokine TNF-α, which can promote the activation and proliferation of T cells. Hyphae differ in cell wall composition. The cell wall molecule GAG is secreted from hyphae and is present in the biofilm. The adhesion ability of A. fumigatus to the cell surface is important for virulence. LkhA is required for biofilm formation by modulating gene expression. During its growth, A. fumigatus produces GT, which is toxic to host cells. LkhA represses the expression of GT clustered genes and thus the production of GT. A. fumigatus also produces proteases to obtain nutrients by degrading macromolecules in the host environment. LkhA negatively regulates the expression of gene(s) for alkaline proteases and thus protease production. The virulence of A. fumigatus in the T cell-deficient zebrafish larva model was reduced by the loss of lkhA.