Fig. 7: ACT001 inhibits PD-L1 expression to enhance neutrophil-mediated antifungal immunity against lethal C. albicans sepsis.

a Immunoblotting analysis of phosphorylation level of JAK2 or STAT3 in mu-PMNs after treatment with ACT001 (40 μmol/L), which were co-stimulated with curdlan (25 μg/well) for indicated time. b The percentage of PD-L1⁺Ly-6G⁺mu-PMNs and PD-L1⁺CD66b⁺Hu-PMNs after treatment with ACT001 at indicated concentrations, which were co-stimulated with curdlan (25 μg/well for mu-PMNs and 50 μg/well for Hu-PMNs) for 12 h. c The percentage of PD-L1⁺ Ly-6G⁺ mu-PMNs in wild-type and Clec7a^−/− mouse stimulated with curdlan (25 μg/well) or yeast (MOI = 1) combined with inhibitor ACT001 (40 μmol/L) for 12 h. d, e ELISA quantification of CXCL1 and CXCL2 in the supernatant of mu-PMNs and Hu-PMNs after treatment with ACT001 (40 μmol/L), which were co-stimulated with curdlan (25 μg/well for mu-PMNs and 50 μg/well for Hu-PMNs) for 4 h. f Naive neutrophils driven by the supernatants of wild-type mu-PMNs stimulated with curdlan (25 μg/well for mu-PMNs and 50 μg/well for Hu-PMNs) combined with ACT001 (40 μmol/L) for 4 h. g–i The percentage of PD-L1⁺ neutrophils (g) and neutrophils (h), and survival and fungal burden of kidney (i) of C. albicans (2 × 10⁵ CFU/mouse)-infected wild-type mice, which were intragastrically treated with ACT001 (200 mg/kg) on day 1 and 3. j In vitro antifungal susceptibility testing results. Data were presented as mean ± SD; n = 3 (b–f), n = 4 (i), n = 6 (g, h), n = 10 (i) biological independent samples. Data were analyzed by unpaired two-sided Student’s t test in d–i, one-way ANOVA adjusted for multiple comparisons in b, c or two-sided log rank (Mantel–Cox) tests in i. Source data are provided as a Source data file.