Fig 1.
Pathways to calcineurin–NFAT activation during endocytosis.
NFAT, nuclear factor of activated T cells. Phagocytosis of zymosan or C. albicans leads to Syk-dependent activation of calcium flux via PLCγ. In contrast, for A. fumigatus, phagocytosis leads to TKR9 and Btk-dependent calcineurin-NFAT activation via PLCγ. This is independent of Syk. For particulate LPS, endocytosis via CD14 leads to PLCγ-dependent calcineurin-NFAT activation.
Fig 2.
Metaforosis—lateral transfer of A. fumigatus during macrophage necrosis.
For 90% of macrophages, phagocytosis of A. fumigatus leads to successful killing of the pathogen and resolution of the inflammatory response. However, if progressive fungal germination occurs, this results in inflammatory macrophage cell death. Under these circumstances, around half of germinating conidia ultimately escape from the dying macrophage. However, in the other half of cases, the dying macrophage is able to transfer the germinating conidium to a bystander macrophage, giving this macrophage a second chance to kill the fungus. This process of lateral transfer, or metaforosis, is highly dependent on calcineurin activation and occurs through a late endocytic compartment surrounded by actin and VASP. VASP, vasodilator-stimulated phosphoprotein.
Table 1.
Important future questions in the field.