Immune set‑points in antifungal immunity: tolerance, inflammation, and exhaustion

The interaction between fungal microbes and the host establishes immune set‑points. These are dynamic thresholds that determine whether immune responses remain tolerant, initiate protective inflammation, or progress toward exhaustion and dysfunction. Understanding how these set‑points are formed, maintained, and disrupted is central to antifungal immunity and to immune regulation more broadly.Fungi pose a unique challenge because they can behave as commensal, opportunistic, and environmental fungal pathogens. Under homeostatic conditions, tolerance mechanisms support coexistence with commensal fungi while preserving the capacity for rapid immune activation when needed. During infection, coordinated innate and adaptive responses, encompassing inflammatory cytokine networks and the activation of myeloid and lymphocyte populations, are required for effective fungal control. These responses must be tightly regulated to clear pathogens while limiting collateral tissue damage. However, persistent fungal exposure, chronic inflammation, or underlying immune dysregulation can shift immune set‑points toward maladaptive states. Chronic inflammation may become self‑perpetuating, cause tissue injury, and undermine immune competence. Conversely, sustained immune activation can drive immune exhaustion and suppressive programs, characterised by checkpoint receptor expression, regulatory circuits, and functional impairment. These shifts weaken antifungal immunity and increase susceptibility to infection. Together, these processes highlight the delicate balance between immune activation and regulation that defines successful antifungal defence.This Research Topic aims to bring together fundamental, translational, and clinical studies that advance our understanding of immune set‑points in antifungal immunity. We welcome work exploring immune regulation across commensal, environmental, and pathogenic fungal interactions including mechanisms of tolerance, inflammation, exhaustion, and immune dysfunction. By integrating mechanistic and clinical perspectives, this collection seeks to establish new conceptual frameworks for immune regulation in antifungal defence. Ultimately, these insights will deepen our understanding of host-fungal interactions and support the development of improved diagnostic, preventive, and therapeutic strategies that maintain immune balance and strengthen antifungal protection.We welcome original research, reviews, and perspectives that advance mechanistic and conceptual understanding of how immune set‑points regulate antifungal immunity. 1. Establishment of Immune Set‑Points: Tolerance and Immune CalibrationStudies examining how fungal exposure, colonization, and the mycobiome shape immune tolerance, immune thresholds, and immune homeostasis. We invite work on immune education, trained immunity, tolerance mechanisms, and the principles governing host-fungal coexistence.2. Inflammatory Activation and Protective Antifungal ImmunityResearch defining the pathways that drive effective antifungal immunity, including innate and adaptive responses, cytokine networks, and tissue‑specific inflammatory programs required for fungal control.3. Immune Exhaustion, Suppression, and Failure of Immune ControlStudies investigating how persistent fungal exposure or chronic immune activation shift immune set‑points toward exhaustion or suppression. This includes checkpoint pathways, regulatory circuits, dysfunctional immune states (including hyperinflammation and autoantibodies), and the mechanisms by which these processes compromise antifungal defence.We particularly encourage interdisciplinary and mechanistic studies that redefine current models of immune regulation and establish new conceptual frameworks for understanding immune balance in antifungal immunity. Topic editors: Ivy M. Dambuza, Roberta Peres Da Silva Source: https://www.frontiersin.org/research-topics/78614/immune-set-points-in-antifungal-immunity-tolerance-inflammation-and-exhaustion