Fig. 5: MICL regulates NET formation during fungal infection.

a, Fluorescence of A. fumigatus hyphae-induced NETs bound to Sytox green in bone marrow-isolated neutrophils from WT and MICL-deficient mice or human neutrophils in the presence of antibodies to MICL. The fluorescence background signal from the unstimulated controls was subtracted from values. Data are a representative example of n = 3 independent experiments, depicted as mean ± s.d. performed in triplicate. The AUC was analysed using an unpaired two-tailed Student’s t-test. WT versus Micl^−/− P = 0.0272 and anti-hMICL versus isotype P = 0.0032. b, Survival of mice following intravenous infection with 10⁶ A. fumigatus conidia (n = 15 mice per group). Pooled data are from two independent experiments, analysed by log-rank test; P = 0.0005. c–e, Brain fungal burdens (c), and serum (d) and brain (e) cytokine levels of mice 2 days after intravenous infection with 10⁶ A. fumigatus conidia. Values are mean ± s.e.m. of pooled data from two independent experiments. n = 12 (c) or n = 8 (d,e) biologically independent mice, analysed using an unpaired two-tailed Student’s t-test. IL-6 WT versus Micl^−/− P = 0.0185 (d) and G-CSF WT versus Micl^−/− P = 0.0492 (e). CFU, colony-forming unit. f, Survival of mice following intravenous infection with 10⁶ A. fumigatus conidia and treated with GSK484 (PAD4 inhibitor). Pooled data are from two independent experiments; n = 14 biologically independent mice, analysed by log-rank test. g, Brain fungal burdens of mice 2 days after intravenous infection with 10⁶ A. fumigatus conidia treated with GSK484 (PAD4 inhibitor) or vehicle control. Values are mean ± s.e.m. of 1 experiment with n = 6 biologically independent mice, analysed by one-way ANOVA with Tukey’s multiple comparisons test. WT vehicle versus Micl^−/− vehicle P = 0.0378, WT + GSK4848 versus Micl^−/− vehicle P = 0.0356 and Micl^−/− vehicle versus Micl^−/− + GSK484 P = 0.0242. *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001.

Source Data