Do fungal pathogens exploit HLA-G-mediated immune tolerance?

Fungal pathogens employ diverse strategies to evade host immunity and establish persistent infection, yet the contribution of immune checkpoint pathways to fungal pathogenesis remains incompletely understood. Human leukocyte antigen-G (HLA-G) is a nonclassical major histocompatibility complex class I molecule with potent immunoregulatory properties. It is capable of suppressing innate and adaptive immune responses through interactions with inhibitory receptors. Although HLA-G-mediated immune tolerance is increasingly recognized in cancer, transplantation, and persistent viral and parasitic infections, its role in fungal disease remains largely unexplored. This review examines the hypothesis that fungal pathogens may exploit HLA-G-mediated immune tolerance to facilitate infection and persistence. Particular attention is given to interleukin-10 and transforming growth factor-β, two immunoregulatory cytokines linked to HLA-G expression that are prominently induced during various fungal infections. The convergence of these pathways provides a mechanistic framework connecting fungal-induced immune regulation with potential HLA-G activity. Establishing this relationship could reveal an underrecognized mechanism of fungal immune evasion and identify opportunities for host-directed therapy.