(470) Investigating Inflammasome Responses to Pathogenic Fungi

Introduction/Rationale: Fungal pathogens are increasingly recognized as important activators of the innate immune system, particularly through engagement of inflammasomes. These are large protein complexes that trigger pyroptosis, an inflammatory cell death resulting in the release of IL-1 family cytokines. Although a large body of evidence demonstrates that diverse fungal species activate inflammasomes, they employ various evasion mechanisms that can limit the level of cell death and IL-1 release.

Methods: Among the inflammasomes, NLRP3 has emerged as a central mediator of antifungal immunity. However, NLRP3 is not regarded as a direct pathogen sensor, but rather integrates signals related to potassium efflux, reactive oxygen species, and lysosomal damage. Given that many cytosolic sensors have defined ligands, a question that remains largely unexplored in the field of fungal innate immunity is whether specific cytosolic detection pathways exist for fungal cell wall components.

Results: Our work aims to understand the molecular mechanisms governing fungal intracellular sensing and inflammasome activation, to provide critical insights into host–fungi interactions and inform the development of therapies for the increasing emergence of invasive and inflammatory fungal diseases.

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