Transient impairment of bacterial immunity in human IRAK-4 deficiency

C Picard; A Puel; C Lung Ku; J Bustamante; M Bonnet; C Soudais; S Dupuis; C Elbim; David Lammas; G Davies; S Al Hajjar; S Al-Jumaah; I Al-Mohsen; A Aderem; A Al-Ghonaium; H Tufenkeji; M-A Gougerot-Pocidalo; G Courtois; A Ozinsky; J-L Casanova

doi:10.1126/science.1081902

Transient impairment of bacterial immunity in human IRAK-4 deficiency

C Picard, A Puel, C Lung Ku, J Bustamante, M Bonnet, C Soudais, S Dupuis, C Elbim, David Lammas, G Davies, S Al Hajjar, S Al-Jumaah, I Al-Mohsen, A Aderem, A Al-Ghonaium, H Tufenkeji, M-A Gougerot-Pocidalo, G Courtois, A Ozinsky, J-L Casanova

Immunology and Immunotherapy

Research output: Contribution to journal › Article

735 Citations (Scopus)

Abstract

Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood and fibroblast cells did not activate nuclear factor kappaB and mitogein-activated protein kinase (MAPK)and failed to induce downstream cytokines in response to any of the known ligands of TIR-bearing receptors. The otherwise healthy children developed infections caused by pyogenic bacteria. These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms.

Original language	English
Pages (from-to)	2076-9
Number of pages	4
Journal	Science
Volume	299
DOIs	https://doi.org/10.1126/science.1081902
Publication status	Published - 1 Jan 2003

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Picard, C., Puel, A., Lung Ku, C., Bustamante, J., Bonnet, M., Soudais, C., Dupuis, S., Elbim, C., Lammas, D., Davies, G., Al Hajjar, S., Al-Jumaah, S., Al-Mohsen, I., Aderem, A., Al-Ghonaium, A., Tufenkeji, H., Gougerot-Pocidalo, M.-A., Courtois, G., Ozinsky, A., & Casanova, J.-L. (2003). Transient impairment of bacterial immunity in human IRAK-4 deficiency. Science, 299, 2076-9. https://doi.org/10.1126/science.1081902

@article{5fc93902bf3d422e9e4392b1465c4b5e,

title = "Transient impairment of bacterial immunity in human IRAK-4 deficiency",

abstract = "Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood and fibroblast cells did not activate nuclear factor kappaB and mitogein-activated protein kinase (MAPK)and failed to induce downstream cytokines in response to any of the known ligands of TIR-bearing receptors. The otherwise healthy children developed infections caused by pyogenic bacteria. These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms.",

author = "C Picard and A Puel and {Lung Ku}, C and J Bustamante and M Bonnet and C Soudais and S Dupuis and C Elbim and David Lammas and G Davies and {Al Hajjar}, S and S Al-Jumaah and I Al-Mohsen and A Aderem and A Al-Ghonaium and H Tufenkeji and M-A Gougerot-Pocidalo and G Courtois and A Ozinsky and J-L Casanova",

year = "2003",

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doi = "10.1126/science.1081902",

language = "English",

volume = "299",

pages = "2076--9",

journal = "Science",

issn = "1095-9203",

publisher = "American Association for the Advancement of Science",

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Picard, C, Puel, A, Lung Ku, C, Bustamante, J, Bonnet, M, Soudais, C, Dupuis, S, Elbim, C, Lammas, D, Davies, G, Al Hajjar, S, Al-Jumaah, S, Al-Mohsen, I, Aderem, A, Al-Ghonaium, A, Tufenkeji, H, Gougerot-Pocidalo, M-A, Courtois, G, Ozinsky, A & Casanova, J-L 2003, 'Transient impairment of bacterial immunity in human IRAK-4 deficiency', Science, vol. 299, pp. 2076-9. https://doi.org/10.1126/science.1081902

TY - JOUR

T1 - Transient impairment of bacterial immunity in human IRAK-4 deficiency

AU - Picard, C

AU - Puel, A

AU - Lung Ku, C

AU - Bustamante, J

AU - Bonnet, M

AU - Soudais, C

AU - Dupuis, S

AU - Elbim, C

AU - Lammas, David

AU - Davies, G

AU - Al Hajjar, S

AU - Al-Jumaah, S

AU - Al-Mohsen, I

AU - Aderem, A

AU - Al-Ghonaium, A

AU - Tufenkeji, H

AU - Gougerot-Pocidalo, M-A

AU - Courtois, G

AU - Ozinsky, A

AU - Casanova, J-L

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood and fibroblast cells did not activate nuclear factor kappaB and mitogein-activated protein kinase (MAPK)and failed to induce downstream cytokines in response to any of the known ligands of TIR-bearing receptors. The otherwise healthy children developed infections caused by pyogenic bacteria. These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms.

AB - Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood and fibroblast cells did not activate nuclear factor kappaB and mitogein-activated protein kinase (MAPK)and failed to induce downstream cytokines in response to any of the known ligands of TIR-bearing receptors. The otherwise healthy children developed infections caused by pyogenic bacteria. These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms.

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DO - 10.1126/science.1081902

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SN - 1095-9203

VL - 299

SP - 2076

EP - 2079

JO - Science

JF - Science

ER -

Transient impairment of bacterial immunity in human IRAK-4 deficiency

Abstract

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