Fig. 7.

TIR-dependent signaling in the patient’s leukocytes. (A) TNF-α secretion by EBV-transformed B cells from controls (n = 4), the IRAK-1–deficient patient, and IRAK-4– and MyD88-deficient patients, left unstimulated or stimulated with R848 (3 μg/mL) and PDBu (10⁻⁷ M) as a positive control. The values shown (means ± SEM) were obtained in three independent experiments. (B and C) PBMCs from healthy controls (n = 3), the IRAK-1–deficient patient, and two IRAK-4–deficient patients were left unstimulated or stimulated with IL-1β (20 ng/mL), PAM-3 (1 μg/mL), PAM-2 (1 μg/mL), FSL-1 (100 ng/mL), LTA (1 μg/mL), LPS (10 ng/mL), MPLA (1 μg/mL), R848 (1 μg/mL), heat-killed S. aureus (10⁷ HKSA per mL), bacillus de Calmette et Guérin, and, as positive controls, TNF-α (20 ng/mL) and PMA/ionomycin (10⁻⁷ M/10⁻⁵ M). The production of multiple cytokines in IRAK-1–deficient PBMCs was evaluated by multiplex ELISA. Cytokine levels are represented as ratios of the response observed in the patient to mean levels in controls. For none of the stimulations tested, the patient showed either no induction or at 0-10% of the controls. (B). IL-6 production, as determined by ELISA (C). The values shown (means ± SEM) were obtained in two independent experiments.