FIG 1.

(A) Fungicidal activities of monocyte-derived macrophages (A); (B to E) cytokine levels on BAL samples (B and C) and produced by PBMCs (D and E) according to the ARNT2_rs1374213 genotype. MDM were stimulated with Aspergillus conidia (1:10), and PBMCs were stimulated with zymosan (5 μg/ml) alone or in combination with lipopolysaccharide (LPS; 100 ng/ml). Supernatants were harvested for cytokine analysis at 24 and/or 48 h. (A) MDM from subjects carrying the ARNT2_rs1374213GG genotype or the ARNT2_rs1374213G allele showed an impaired capacity to kill A. fumigatus conidia compared with that of carriers of the AA genotype (AA genotype, 59.92% of conidia killed, versus GG genotype, 43.61% [P = 0.0176], or AA genotype, 59.92%, versus GA + GG genotype, 46.27% [P = 0.0122], respectively). BAL samples from IA patients carrying the ARNT2_rs1374213GG genotype had a significantly decreased release of IL-1β (B) and a significantly exacerbated production of IL-8 (C) in comparison with those of patients carrying the AA genotype or the A allele [P_{IL-1β (AA versus GG)} = 0.042 and P_{IL-1β (AA + AG versus GG)} = 0.026; P_{IL8(AA versus GG)} = 0.0061 and P_{IL8 (AA + AG versus GG)} = 0.0024, respectively]. (D) After stimulation with zymosan (ZYM) for 24 h, PBMCs from carriers of the ARNT2_rs1374213GG genotype (n = 3) showed a significantly increased production of TNF-α compared with that of subjects carrying the A allele [n = 18; P_{TNF-LPS (24 h)} = 0.017, P_{TNF-ZYM (24 h)} = 0.068 P_{TNF-LPS + ZYM (24 h)} = 0.001] (Fig. 2D). (E) Similarly, after stimulation with zymosan for 48 h, PBMCs from carriers of the ARNT2_rs1374213G allele (n = 6) showed a significantly increased production of IFN-γ [n = 14, P_{IFN-γ–LPS (48 h)} = 0.042, P_{IFN-γ–ZYM (48 h)} = 0.045, and P_{IFN-γ–LPS + ZYM (48 h)} = 0.040].