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Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor–dependent innate antiviral immune responses  Douglas R. McDonald, MD, PhD,

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Presentation on theme: "Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor–dependent innate antiviral immune responses  Douglas R. McDonald, MD, PhD,"— Presentation transcript:

1 Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor–dependent innate antiviral immune responses  Douglas R. McDonald, MD, PhD, Daniel Brown, MD, Francisco A. Bonilla, MD, PhD, Raif S. Geha, MD  Journal of Allergy and Clinical Immunology  Volume 118, Issue 6, Pages (December 2006) DOI: /j.jaci Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

2 Fig 1 Homozygous IRAK-4 mutation in the Genomic DNA sequence of exon 8 of IRAK-4 from the patient and his parents. A, Red arrow indicates the presence of the C to T mutation in exon 8 of IRAK-4. B, Representation of the mutant IRAK-4 protein. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

3 Fig 2 Impaired IL-1–induced p38 MAPK and IκBα phosphorylation in PBMCs from IRAK-4–deficient patient. PBMCs obtained from a healthy control and the patient were stimulated with IL-1 or PMA plus ionomycin (P/I) for the indicated times. Lysates were subjected to Western blotting with antiphospho-p38 MAPK, antiphospho-IκBα, and anti-TRAF6 as a protein loading control. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

4 Fig 3 Impaired TLR-induced TNF-α production in by PBMCs from IRAK-4–deficient patient. Normal and patient PBMCs were stimulated with medium, PAM3CSK4 (TLR1/2), Poly I:C (TLR3), LPS (TLR4), Flagellin (TLR5), 3M-13 (TLR7), 3M-2 (TLR8), ODN2216 (TLR9), or PMA plus ionomycin (P/I), and TNF-α was measured in cell culture supernatants. The data shown are representative of 2 experiments. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

5 Fig 4 Impaired TLR 3, 7, 8, and 9–induced IFN-α production in the IRAK-4–deficient patient. A, Normal and patient PBMCs were stimulated with medium, IFN-β, PMA plus ionomycin, or TLR ligands as described in Fig 3, and IFN-α was measured in cell culture supernatants. B, PBMCs from the patient (n = 4), his parents (n = 2 each), and normal controls (n = 4) were stimulated with medium or Poly I:C. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

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