Manipulation of Host Nuclear Transport Pathways in Fungal Infections: Current Evidence and Future Directions

The nuclear pore complex (NPC), a large multiprotein structure embedded in the nuclear envelope of eukaryotic cells, serves as the only communication channel between the cytoplasm and the nucleus. By controlling entry and exit from the nucleus, NPCs ensure the smooth functioning of nuclear and cellular processes. Defects in proper nucleocytoplasmic transport are associated with cancers and neurodegenerative disorders. Proper nucleocytoplasmic transport also plays a key role in regulating host immune responses. Viral and bacterial pathogens are known to evade the host immunity by altering the crucial exchange of molecules across the NPCs. However, whether the mammalian fungal pathogens alter the host nuclear transport machinery to establish infection remains largely unknown. In this review, we first present an overview of how mammalian viral and bacterial pathogens manipulate NPCs and bidirectional traffic through NPCs to evade host immunity. This is followed by a section discussing plant fungal pathogens that are known to manipulate the flow of immunity-related molecules across NPCs. Finally, we discuss the mammalian fungal pathogens, in which host nucleocytoplasmic transport plays a key role in host immunity. Here, we highlight that the fungal manipulation of host molecular traffic across NPCs remains largely unexplored. We further argue that this lack of evidence should be treated as a substantial knowledge gap and that these mechanisms need to be explored in depth in the future. Focused research in this direction could lead to the development of new antifungal strategies, thereby saving millions of human lives worldwide