Table 1.
Antifungal signaling pathways discovered in the last 5 years.
| Target | Mode of action | Spectrum of activity |
|---|---|---|
| TRIM31 (26) | TRIM31 interacts with SYK and catalyzes polyubiquitination of SYK. Lack of TRIM31 in bone marrow-derived dendritic cells and macrophages inhibits SYK-mediated signaling pathways. | C. albicans |
| MYO1F (25) | MYO1F recruit adaptor protein AP2A1 to promote fungus-induced acetylation of α-microtubulin, and acetylated α-microtubulin promotes Syk and card 9 translocation from the plasma membrane to the cytoplasm to activating antifungal signaling. | C. albicans |
| Dok3 (27) | downstream of kinase 3 (Dok3) recruits protein phosphatase 1 (PP1) to dephosphorylate Card9, suppressing Card9 signaling. | C. albicans, |
| Commensal C. albicans ( 28) |
intestinal colonization with C. albicans drives systemic expansion of fungal-specific Th17 CD4 T cells and IL-17 responsiveness by circulating neutrophils, which synergistically protect against C. albicans invasive infection. | C. albicans, |
| STIM1 (29) | STIM1 deletion in all immune cells increased susceptibility to C. albicans infection in the mucosa. STIM1 deletion reduced the production of Th17 cytokines, which are important for antifungal immunity, as well as the expression of genes involved in various metabolic pathways, including Foxo and HIF1 signaling, which regulate glycolysis and oxidative phosphorylation. | C. albicans |
| Kupffer cells (30) | Kupffer cells in the liver have a prominent function in the capture of circulating Cryptococcus neoformans and C. albicans, thereby reducing fungal dissemination to target organs. | C. neoformans and C. albicans |
| Xp38γ and p38δ (31) | p38γ and p38δ regulate the AK1-TPL2-MKK1-ERK1/2 pathway in macrophages, which is activated by Dectin-1 splicing. In mice, p38γ/p38δ deficiency increases the antifungal capacity of neutrophils and macrophages by increasing the production of ROS and iNOS. | C. albicans |
| fungal melanin (14) | fungal melanin is an essential PAMP required for the Warburg shift and the ensuing immunometabolic responses in macrophages. | C. albicans and A. fumigatus |
| antifungal IgG (18) | The intestinal commensal fungus C. albicans is a major inducer of antifungal IgG. B cells expand in extraintestinal lymphoid tissue and produce systemic antibodies to prevent disseminated fungal infections. Production of antifungal IgG is dependent on CARD9 and CARD9CX3CR1 macrophages. | C. albicans and C. auris |
| Dock2 (32) | After fungal stimulation, activated SYK phosphorylates DOCK2 to promote the recruitment and activation of RAC GTPase, which then increases ROS production and downstream signaling activation to clear the fungus intracellularly. | C. albicans |
| JNK1 (33) | JNK1 activation suppresses anti-fungal immunity in mice. NK1 deficiency leads to significantly higher induction of CD23, a novel C-type lectin receptor, through NFATc1-mediated regulation of the CD23 promoter. | C. albicans |